Interventional News Issue 81—March 2021 US Edition

March 2021 | Issue 81

Featured in this issue:

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IR Services IRs call on WHO

Profile Parag Patel

Insights from the SIR president-elect page 24

Ablation 2.0: Improved precision as interventionalists approach A0 Ablation is entering a new era of increased precision and quantification, the interventional radiology (IR) community argues, with outcomes that match or surpass those of surgery.

Whilst reaching equipoise with their surgical counterparts has been a goal for interventional radiologists since the advent of ablative treatments for cancer, some expert interventionalists claim that the increased precision of modern thermal ablation techniques, coupled with improvements in radiology mean physicians are often treating smaller volume tumours. This now positions the procedure as the “definitive” treatment for select patients in some cancers.

Several clinical trials—including the ACCLAIM, COLLISION, and COVER-ALL trials—are currently underway, and aim to bolster the evidence-base demonstrating favourable patient outcomes from thermal ablation.

“W

e are now talking about Varian, a radiotherapy company, which ablation 2.0,” past in 2019 itself acquired Endocare, a Society of Interventional company specialising in cryoablation Oncology (SIO) president Stephen and microwave ablation, and Alicon, Solomon (Memorial Sloan Kettering a provider of embolic therapy for liver Cancer Center, New York, USA) says. cancer treatment.

“Ablation 1.0”, in his eyes, is the basic Cascination is another company concept underpinning the minimally offering an over-arching solution invasive procedure: put a needle in, for ablation, with products designed use image guidance, burn or freeze for imaging, planning, navigation, the cancerous tissue to destroy it. “But validation, treatment, and treatment ablation 2.0,” he explains, “means that verification. Breen believes this we are focusing more on precision, on is the direction industry is taking, margins, and specifically the road to A0 and represents a shift away from a [where all tumour cells are eradicated].” more modular approach where one When discussing soft and organisation may only offer products for hardware advances in ablation, part of this pathway.

David Breen (University Hospital of Southampton, Southampton, UK) Developing improved adopts the framework of “planning, planning software execution, confirmation”. Planning Several different groups around the uses preprocedural scans to map out world are working on developing probe positions and angles, along with planning software for ablation estimation of the ablation zone—all treatments with the goal of obtaining the steps taken ahead of performing the a predictable technical outcome. “In ablation. Execution is the act of probe order to do this effectively,” current SIO Intra-ablation feedback: software positioning, sometimes using guidance president Matthew Callstrom (Mayo using biomechanical deformable tools. The final stage, confirmation, Clinic, Rochester, USA) explains, “it is registration volumetric imaging involves determining the adequacy of necessary to have accurate registration treatment margins in order to verify complete ablation.. software for all phases of the ablation, including planning, “Of these three stages, confirmation and perhaps intraprocedural evaluation of device placement, and planning are the two that are beginning to enter a higher postprocedural measurement of the margins of the level of engineering maturity and reliability,” Breen ablation. This approach will transition thermal ablation explains. Guidance tools, as they currently stand, must still from a subjective technical endpoint to an objective be used with careful operator insight”. technical endpoint. I think the exciting aspect of this is that The upcoming European Conference on Interventional many efforts are underway and will become more widely Oncology (ECIO; 10–13 April, online) is hosting a session available to proceduralists.” entitled “Different ways of killing cancer and why we need From the department of Interventional Radiology at all of them”, which explores advances in ablation.

The University of Texas MD Anderson Cancer Center In a further sign of the times, several large companies (Houston, USA), Bruno Odisio tells Interventional are positioning themselves to buy smaller businesses News that he and imaging physicist Kristy K Brock have operating in this space. In 2020, for example, imaging received a National Institute of Health (NIH) grant for behemoth Siemens Healthineers acquired all shares of Continued on page 2

COVID-19 Rising to the challenges ahead page 34

IO solutions for patients with brain tumours: Intraarterial delivery of chemotherapy improves survival The use of intra-arterial (IA) delivery for the treatment of malignant brain tumours is safe and provides clinical benefits in terms of survival when used with the appropriate therapeutic agents, according to a small, phase II study presented at the virtual European Conference on Interventional Oncology (ECIO; 24 February, online). Delivering these results, Gérald Gahide (Sherbrooke University Hospital, Sherbrooke, Quebec, Canada) told delegates that while the study demonstrated the technical feasibility and safety of this application, “there is a dire need for designing multicentre, prospective, phase III studies to properly compare IA and intravenous [IV] treatments”.

GLIOBLASTOMAS AND LYMPHOMAS, both types of primary malignant cerebral nervous system tumours, are quite rare, with an incidence of 8.85 out of 100,000 and seven out of 1,000,000, respectively, of the adult population in the USA. Standard treatment for the former tumour is cytoreductive surgery, where the interventionalist takes a debulking strategy of removing as much of the tumour as possible. When used in conjunction with complementary external beam radiation and chemotherapy, the median survival time is 14.6 months. Gahide told delegates: “Unfortunately, it is impossible to remove all of the tumour because it is a very infiltrated disease and relapse is the norm, and five-year survival is less than 10%”.

Commenting on the treatment of cerebral nervous system lymphoma, he said: “The only point that people agree on is that there should be high IV [intravenous] dose of methotrexate (3g/m2) during the induction, but, as of today, there is no consensus regarding what other drugs to use for induction or consolidation.”

Survival improved with intraarterial delivery

In their prospective, phase II study, Gahide and colleagues treated 51 patients at first (n=39) Continued on page 4

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March 2021 | Issue 81

Thermal ablation

Ablation 2.0: Improved precision as interventionalists approach A0 Continued from page 1

the development of a dedicated liver ablation planning and assessment software. “We are using this software to simulate treatment because we know that when we do an ablation, the most important thing that we can do is to safely cover the tumour with adequate margins,” he explains.

Odisio and colleagues are enrolling for a phase II trial (COVER-ALL) to study how well software-aided imaging works in confirming tumour coverage with ablation on patients with liver tumours. The primary objective of the COVER-ALL trial is “To evaluate if the intraprocedure feedback of a biomechanical deformable registration volumetric image method during percutaneous ablation will increase the minimal ablation margins on a threedimensional (3D) computed tomography (CT)-generated analysis.”

Clinicaltrials.gov registers: “The current standard for targeting tumour cells and evaluating the outcome of a liver ablation procedure is a visual inspection of the pre- and postprocedure computed tomography (CT) scans. Softwareaided imaging systems may help to improve the accuracy and effectiveness of liver ablation.”

Prior to receiving the NIH grant for the COVERALL study, Odisio and Brock conducted a preliminary, retrospective analysis using their software to make a fusion image of the preprocedural and postprocedural CT images. The software utilises a biomechanical model to align the images, which Odisio says allows them to account for patient breathing, positioning, and tissue desiccation associated with the ablation itself. “We noticed that many times, our simple visual inspection of the CT scans before and after the ablation gave us a false sense of confidence regarding getting the entire tumour. In fact, most patients who had recurrence after the ablation—there were not that many of them—about 80% of them we did not cover the tumour. So, it is not a recurrence, but it is residual disease that we left behind. That was our motivation to use the software. Using the software with biomechanical modelling negates the issues with trying to decipher simple axial imaging in a complex 3D environment.”

He adds that it is very hard to analyse the imaging data intraprocedurally: “You have a very constrained timeline; you have too much data for you to run. Our software uses artificial intelligence [AI] and a biomechanical model to analyse the data on probe placement and ablation margins during the liver ablation. We hope that this will solidify the idea that using software really helps to improve patient endpoints.” This work is part of the Image Guided Cancer

Therapy (IGCT) Research Program run through The University of Texas MD Anderson Cancer Center.

Luigi Solbiati and his team at Humanitas University in Milan, Italy, have also developed software to aid ablation (Ablation-fit, R.A.W. Srl). “If interventional radiologists wish to compete with surgeons, the availability of software enabling an accurate comparison of pre- and postinterventional CT or magnetic resonance imaging (MRI) scans must become mandatory and routinely employed,” Solbiati opines.

Describing the software to this newspaper, he comments: “It is based on automatic segmentation of liver parenchyma and major blood vessels, semi-automatic segmentation, and reconstruction of tumoural targets and post-ablation necrotic areas and [employs a] non-rigid, fully automatic registration of pre- and postablation CT scans that allows us to deform the liver parenchyma section by section, based on the location of intrahepatic blood vessels. This allows for an extremely precise image fusion regardless of differences in body position, respiratory motion, or liver deformation. In addition, in very short time (five to 10 minutes) the software calculates the percentages of residual, unablated volumes of both the target tumour and predetermined 3D safety margin.”

In a retrospective study of 90 hepatocellular carcinomas (HCCs) that had undergone microwave ablation with apparent technical success and followed for at least one year, published in the International Journal of Hyperthermia, Solbiati et al demonstrated that, if they could have used this software, they would have discovered incomplete treatments at 24-hour CT scan (enabling immediate retreatment) in 76.6% of the HCCs that actually had local tumour progression at one year.

In a clinical study recently published in European

Software-aided imaging systems may help to improve the accuracy and effectiveness of liver ablation.”

Radiology of colorectal liver metastases that have undergone radiofrequency ablation (RFA) with volumetric assessment of the periablational safety margin performed using this software, it was proved that the safety margin assessment was the only independent predictor of local tumour progression, and that at least 90% of a 6mm circumscribed 3D safety margin was required to achieve complete ablation.

“Ablation-confirmation software like this can be used in different modalities,” Solbiati says. “When ablations

News in brief

The latest stories from the interventional world

n CVIR ENDOVASCULAR LAUNCHES NEW PODCAST IN THE INTERVENTIONAL SPACE: The journal CVIR Endovascular launched its own podcast in December 2020, to discuss endovascular and interventional interventions.

Jim Reekers

For more on this story go to page 5. n POSITIVE FIRST-TIME DATA PRESENTED AT LINC FOR IN.PACT AV DCB AND ELLIPSYS SYSTEM: New data presented for the first time at LINC 2021 support the use of drug-coated balloons (DCBs) as a treatment for dysfunctional arteriovenous fistulas (AVFs). The audience also heard the case for percutaneously-created AVFs with the Ellipsys vascular access system (Medtronic).

For more on this story go to page 11. n PATIENTS WITH STROMAL ENLARGEMENT OF THE PROSTATE BENEFIT THE MOST FROM PAE, TWOYEAR STREAM TRIAL DATA REVEAL: Prostate artery embolization (PAE) is a good treatment option for patients with benign prostatic hyperplasia (BPH) with minimal complications, according to the 24-month results of the STREAM trial, which the study authors claim affirms the use of the minimally invasive procedure.

For more on this story go to page 19.

Sandeep Bagla

Continued on page 4

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March 2021 | Issue 81

Latest news

Ablation 2.0: Improved precision as interventionalists approach A0 Continued from page 1

are performed in sonographic rooms under the control of contrast-enhanced ultrasound (US), potentially integrated with real-time US-CT/MRI image fusion, ablation-confirmation software like this can be used only after the end of the treatment. In this situation, a level of assessment closer to that achieved by pathologists after surgical resection can be obtained, but if incomplete treatment or insufficient ablative margins are seen, the procedure will have to be repeated, as it would occur for surgery.

If ablations are performed under US guidance (or CT guidance) in the CT room (as would be recommended nowadays), the software would be used immediately, during the procedure, and the treatment could be immediately completed if partial or with insufficient ablative margins. This would represent even an advantage over surgical resection.

“In addition, this kind of software can trace out the ideal path to the portion of tumour to be treated, thus significantly facilitating the completeness of the procedure.

“In the near future, it is hoped that such easily usable and extremely fast software will be increasingly employed in interventional departments, while we are currently working to extend their applicability also to extrahepatic organs (kidney, lung, lymph nodes, prostate) and to MRI scans.”

ACCLAIM and COLLISION: Trials to watch

The SIO is also currently planning a multicentre clinical

trial—the ACCLAIM trial—that incorporates software that looks at margins into the ablation, and which will aim to determine if achieving complete margins during an ablation equates to procedural success, assessed through disease progression or recurrence postprocedurally. Constantinos Sofocleous (Memorial Sloan Kettering Cancer Center, New York, USA) will be the principal investigator.

“The ACCLAIM trial will be the first liver ablation trial to use a well-defined objective technical outcome measure as a critical aspect of the trial design,” Callstrom tells Interventional News. “We anticipate that this will help drive adoption of this approach as the standard for liver mass ablation”.

Sofocleous comments: “The ACCLAIM trial is a single-arm, prospective, multicentre, international phase II study where thermal ablation will be offered in patients with limited number and relatively small CRC [colorectal cancer] liver metastases. A mandatory requirement for enrolment in the trial is the use of real-time 3D software to assess the ablation zone and show that the target tumour has been completely covered with ideally 10mm and not less than 5mm of minimal ablation margins. The study hypothesis is that if ablation margins are larger than 5mm, local progression-free survival at 12 months after ablation will be over 85%.”

Another hotly anticipated

IO solutions for patients with brain tumours: Intra-arterial delivery of chemotherapy improves survival Continued from page 1

or second (n=12) relapse glioblastoma with IA carboplatin (400mg/m2) and melphalan (10mg/m2). Median overall survival from initial diagnosis was 23 months, and the median survival time from study entry was 11 months.

Progression-free survival after IA treatment initiation was 4.2 months.

The investigators considered this therapeutic strategy “a great second line regimen in the treatment of recurrent malignant gliomas”.

In terms of safety, Gahide et al conducted a systematic review of the files of all patients treated with cerebral IA chemotherapy at their institution since January 2000.

Follwoing this analysis, Gahide concluded: “Overall, the technique is safe. There is the potential for local neurotoxicity related to delivery of higher concentrations of drugs in the cerebral tissue remains. The administered drugs must thereby be carefully selected. We must emphasise, however, that the osmotic blood-brain barrier disruption [OBBBD] process per se is not toxic. The subsequently infused drugs are the culprits when faced with

neurotoxicity. To date, OBBBD offers some of the best results in most clinical studies for the treatment of brain tumours.”

The bloodbrain barrier

One of the main reasons explaining the poor prognosis and responses to treatment is the presence of the blood-brain barrier that presents “significant obstacles” to drug delivery, Gahide explained.

The blood-brain barrier selectively transports substances into the brain; according to reports in the literature, 98% of small drugs do not cross the blood-brain

trial is the COLLISION trial. Sofocleous tells this newspaper: “I am very interested to see the results of the COLLISION trial that compares thermal ablation to resection for well-selected small colorectal liver tumours.

“This trial is now enrolling in The Netherlands, and will address a lot of the questions that exist for the value of ablation.

“I am particularly interested to find out whether the trial will provide high-level evidence about thermal ablation and whether this treatment can be equally effective and potentially safer than limited resection as a local curative therapy for CRC liver metastases.”

In an additional attempt to further improve margin confirmation, Solomon informs this newspaper that he and Sofocleous are conducting research into performing biopsies around the edges of the tumour intraoperatively, in order to gain a quick pathological assessment of whether or not any cancer cells are left alive.

“This allows them to be more adaptive during the procedure: “If, during the procedure, we find there is still live tissue, we would do something about it. If the software shows us that the margins are close, maybe we would expand it [the ablation zone] a bit.

“All of these things allow us to finesse and improve our results.”

Matthew Callstrom

barrier. “Because of these restrictive entities, the role of potentially active chemotherapeutic agents remains marginal in the treatment of malignant astrocytomas,” Gahide said.

IA drug delivery can improve the intratumoural concentration of chemotherapeutic agents. According to Gahide, the technique is “quite straightforward”.

His team take a femoral approach: “It is a conscious sedation,” he explained, “and we place a catheter in to the carotid or the vertebral artery, depending on the location of the tumour.” Angiography is used to confirm catheter position and the integrity of the cerebral arteries. Chemotherapies are infused with an automated injector.

Treatment takes place every four weeks (representing one cycle) for up to 12 cycles after a monthly MRI scan.

Another way of circumventing the

Overall, the technique is safe. [...] The administered drug must be carefully selected.”

Patient with a glioblastoma treated intra-arterially in 2008 showing no recurrence at nine-year follow-up

blood-brain barrier is to open it. “In order to improve on the delivery obtained with IA infusion, the idea of osmotic manipulations for transiently opening the blood-brain barrier has been explored. IA infusion of a hyperosmolar agent causes a rapid diffusion of fluid out of the cells, shrinkage of the endothelial cells, and widening of the tight-junctions. Of the many hypertonic solutions with potential to disrupt the blood-brain barrier, mannitol is the typical choice in both preclinical and clinical studies. This increase in blood-brain barrier permeabilisation is transient in the ipsilateral hemisphere and lasts from 30 minutes to two hours.”

It has been reported in the literature that IA infusions with blood-brain barrier disruption increased the intratumoural concentration of carboplatin 18-fold compared with IA administration alone, and 320-fold compared with IV.

Issue 81 | March 2021

Paediatric IR

CVIR Endovascular launches new podcast in the interventional space The journal CVIR Endovascular launched its own podcast in December 2020, to discuss endovascular and interventional interventions, and to promote the Cardiovascular and Interventional Radiological Society of Europe (CIRSE)’s open access journal. The podcast, hosted by Editor-in-chief Jim Reekers (Amsterdam UMC, Amsterdam, The Netherlands), takes place every other month, and highlights articles published in CVIR Endovascular, as well as featuring interviews with contributing authors.

INTERVENTIONAL NEWS discusses the new podcast with Reekers, and how he believes it will transform communication and education within interventional radiology (IR) through a broadening of the discursive channels.

Why is it timely to launch a podcast now, and what are your hopes for this platform?

CVIR Endovascular is a platform for IR publications, but also for ideas and discussions. Since the postponement of many meetings due to the pandemic, we need a new way to communicate and to exchange our IR narratives, as narratives have always been an important part of this unique and innovative medical specialty. Podcasts are a great way to get our message out, especially to millennials, as you can listen to a podcast when you want, and wherever you want.

You can listen whenever you want, commuting, doing the dishes, cooking, just when you want. A podcast is like a friend and not like an aggressive salesperson, it does not speak in headlines. It is thoughtful and contemplative, something we all need in this complex world.

the amazing technical skills, but the real core of IR is being a good and thoughtful doctor for your patients. A podcast does away with the dominant visual factor of current IR communications; as such, having a concurrent CVIR Endovascular podcast episode alongside an article will enrich the paper.

What sort of content can your audience expect from the podcast, and what in the next few months are you specifically excited to discuss?

What can listeners expect in the future?

The podcast will highlight articles published in the journal, as well as hot topics, via interviews with many of our authors and a number They will be complementary of leaders in the field of in the sense that the podcast endovascular interventions. will enrich the journal and the CVIR Endovascular is a journal publications with additional that promotes directions and background information. It Jim Reekers ideas through editorials and will create a community of is therefore a forerunner. The young interventional radiologists around podcast will do exactly the same—it will the journal. make you think and sharpen your mind.

How will the podcast and the journal complement each other?

What is it about the medium of a podcast that appeals/ what benefits are there to this format beyond the journal?

Narratives through podcasts are a relaxed way to communicate a message; it does not have the in-your-face nature of social media, you can consume it at your own pace.

What developments in endovascular and vascular interventions are underreported, and how is CVIR Endovascular giving a platform to these topics?

Endovascular interventions are driven by the hype of the day, for example with all the drug-eluting technologies and

Paediatric interventional radiology in the spotlight: “There is still much more to be done” In an effort to raise the profile of paediatric interventional radiology (PIR), CVIR Endovascular Editor-in-chief Jim Reekers (Amsterdam UMC, Amsterdam, The Netherlands) has invited Alex Barnacle (Great Ormond Street Hospital, London, UK) and Anne Marie Cahill (The Children’s Hospital of Philadelphia, Philadelphia, USA) to guest edit the journal’s first thematic series on the topic.

B

arnacle and Cahill commissioned four review articles, which they say “detail the latest evidence for a range of complex interventions in children, demonstrating current best practices in this highly specialised field”.

They write: “These reviews illustrate that many of the latest advances in adult interventional radiology [IR] are applicable in children, despite the concerns of many adult IR practitioners that such interventions may be too risky or perhaps futile. Each paper, however, also highlights the frustrations common to every paediatric interventional radiologist. These include the limited evidence base available to date, the lack of paediatricsized equipment, and the challenges of developing and maintaining IR competencies with small caseloads, often focussed in only a few specialised centres.”

They note that the specialty has come a long way since the early 1980s. According to Barnacle and Cahill, the first PIR workforce survey in 2007 identified “just 110 PIRs practising worldwide, rising to 177 in a follow-up survey 10 years later”. However, in 2020, more than 600 delegates from 22 countries registered for the Society for Pediatric Interventional Radiology (SPIR) annual congress. The editorialists suggest

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that this is “in part due to the advantages of new online conference accessibility during the COVID-19 pandemic”, but that this “groundswell of interest may be influenced by increasing visibility of the speciality through the work of publications such as this [CVIR Endovascular] and organisations such as SPIR, but we believe it also speaks to a growing interest.”

They conclude their editorial with a call to action: “It is imperative that we strive to eliminate the inequality that means the vast majority of children even in developed countries are denied modern, minimally-

I think it is important to become a friend of the CVIR Endovascular podcast, to reset your mindset, and to step out of the IR rollercoaster when you listen.

A podcast is like a friend and not like an aggressive salesperson, it does not speak in headlines. It is thoughtful and contemplative, something we all need in this complex world.”

invasive, safe, and highly effective IR procedures that are routinely offered to adults.”

Interventional News spoke with Barnacle to gain insights into the urgency and nature of future PIR work.

What have been the pivotal developments in PIR research and clinical practice since its inception?

Over time, we have shown that there is far more that is possible in small children than even we could have imagined. PIR has changed the management of a number of diseases and provided minimally invasive options for thousands of children who would otherwise not have been offered treatment or would have undergone far more invasive surgery.

What areas of PIR do you feel are particularly under-researched?

It is a real challenge to trial interventional oncology (IO) treatments in children because almost all patients are on protocols that do not include IO options. PIR is where adult IR was 20 or 30 years ago, only being given access to patients who have failed most other interventions. This means that the data are sketchy and our patient cohorts are skewed. In time, we hope to see the oncology organisations show greater confidence in the aims we are pursuing.

What are the biggest challenges to PIR currently?

Anna Marie Cahill and Alex Barnacle

The biggest hurdle outside of North America is getting hospitals to recognise what PIR can do when it is a fully resourced service. Most centres are not aware of what we can deliver or the benefits we bring. We need more training schemes, more consultant posts, and the commitment to building PIR in several centres in each country, so that children everywhere have access to minimally-invasive, effective IR treatment options.

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March 2021 | Issue 81

Global IR

Interventional radiologists call on WHO to address the “dramatic lack of IR services” in low income countries The European Trainee Forum of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the Residents, Fellows, and Students section of the Society of Interventional Radiology (SIR), the Society of African Interventional Radiology & Endovascular Therapy (SAFIRE), and Road2IR—a collaborative effort between several partner institutions aiming to build self-sustaining interventional radiology (IR) training programmes in East Africa—have published an open letter to the World Health Organisation (WHO) in CVIR Endovascular, calling for an increase in the efforts to understand the needs of low income countries regarding image-guided therapies.

I

n what participants hope marks “the beginning of a great collaboration between the WHO and the IR community”, several letter signatories first met with Adriana Velazquez Berumen, group lead for medical devices and in vitro diagnostics at WHO, online on 23 October, to discuss IR and service development in low income countries. Interventional News understands that these remote conversations are ongoing, and that an online petition is in the pipeline “to continue raising awareness and increase the pressure on the WHO to do something about this [lack of IR provision in lowincome countries]”.

First author of the CVIR Endovascular letter Yi Yang (Aventura Hospital and Medical Center, Aventura, USA) and colleagues say that the intent of the address is “to initiate a discussion on and collaboration in addressing the dramatic lack of interventional radiology services in low income countries and the lack of associated data”.

The letter is also approved and supported by Andrew Kesselman (RAD-AID International), Susan Jackson (Western Angiographic and Interventional Society), Kartik Ganga and Sreenivasa Raju (both Indian Society of Vascular and Interventional Radiology), Gerard Goh (Interventional Radiology Society of Australasia), Murray Asch and Kevin Shixiao He (Canadian Association for Interventional Radiology), and Karin Euler (Canadian African Health Care Alliance— Tanzania).

The authors write: “Prompt publication of countless dedicated research articles, public education through news outlets and social media on preventive measures, and initiation of vaccine development within weeks of the COVID-19 outbreak highlight the many benefits of global connectivity and collaboration. Yet, these times of fear and stress reveal the persistent chasm of racial inequality, healthcare inequity, and social injustice that have plagued humanity for centuries. These inequalities extend into almost every facet of medicine, but nowhere is the disparity more extreme than in minimally invasive treatment options available to patients in high-income countries and the near-complete lack thereof in most low- and middle-income countries (LMICs). “[…] There are several hurdles to the implementation of IR in LMICs, including the sparsity of baseline data, limited access to equipment, and lack of training. In order to facilitate effective IR training and adequate supply of IR equipment, there is a critical need for improving and updating the ‘WHO Global Atlas of Medical Devices’.”

Speaking to Interventional News about the significance of a collaboration between the WHO and the IR community, immediate past chair of CIRSE’s European Trainee Forum and past chair of the British Society of Interventional Radiology (BSIR) trainee committee, Gregory Makris (Guy’s and St Thomas’​ NHS Foundation Trust, London, UK), a senior author of the open letter, comments: “This letter is part of an effort to increase awareness around this very important issue.

During the last five years there has been significant

effort in increasing the presence of IR in Africa, but we now need more structured support to take these efforts to the next level. We have to make people understand that even standard life-saving procedures like a nephrostomy insertion or a drain of a liver abscess are currently not possible due to the luck of expertise and kit. The scale of the problem, as well as its significance, is massive, and that is why it is important to have a collaboration between international IR societies, the WHO, and the medical devices industry to address the various issues in lack of training, manpower, and supply chain/kit.

We are planning to start an online petition within 2021 in order to reach even more people and get people interested in our cause.

Introducing IR in Africa can have a major impact in raising healthcare standards given the multidisciplinary nature of our specialty. We hope for your support.”

Updating the WHO Global Atlas of Medical Devices

The WHO Global Atlas of Medical Devices, the most recent iteration of which was published in 2017, is a report presenting the global status of national medical device policies and the availability of medical device information, regulations, assessments, procurement, and donation guidelines, as well as the density of high cost medical equipment and guidance documents available at country level.

Its authors say that the aim of the publication is “to raise awareness and bring evidence of the indispensable safe and good use of appropriate, affordable, and quality medical devices in healthcare delivery to achieve better health outcomes”.

Data included in the WHO Global Atlas of Medical Devices come from a 2013 Baseline Country Survey on Medical Devices (to which 177 countries responded), a 2015 global health technology assessment survey (conducted by government or national institutes), and a 2016 study analysing medical devices regulatory frameworks. The information collected by the surveys and studies was then processed into a comprehensive

database that includes statistical analyses of more than 100 aspects related to medical devices evaluated with respect to welfare indicators, such as World Bank income groups, health expenditure, Human Development Index and WHO regions.

However, signatories of the recent CVIR Endovascular letter point out that the WHO document does not assess several medical device and equipment categories “that are integral for diagnosis, treatment, and follow-up of patients by minimally invasive means”.

Specifically, they request the following be included in future WHO Global Atlas of Medical Devices versions: “Ultrasound: As a non-ionising imaging modality, ultrasound is the ideal first-line imaging tool in obstetrics, paediatrics, trauma triage, and is essential for breast cancer diagnosis, biopsy, and follow-up.

Ultrasound is used in over 90% of IR procedures to guide percutaneous biopsies, vascular access, and drainage procedures.

“Fluoroscopy: As a dynamic, X-ray based, real-time imaging modality, fluoroscopy is the other most essential imaging tool used in IR. With fluoroscopy, interventional radiologists can navigate wires and catheters to almost any place in the body in order to perform embolizations in the setting of haemorrhage, limb salvage from peripheral arterial disease, extract clot in the setting of stroke or pulmonary emboli, and administer radio- and chemotherapy locally. These procedures are often life-saving and significantly less invasive than their surgical alternatives.

“Systems for Reviewing Imaging: Determining the availability of PACS (Picture Archiving and Communication System), EMR (Electronic Medical Record), and/or access to a viewing box or written medical records which are paramount for initial evaluation and follow-up of the patient’s medical history, management planning, and disease status over time.”

They expand: “The availability of these data measures will clarify the global distribution of diagnostic and therapeutic imaging and procedural devices. This will allow IR societies, academic institutions, researchers, educators, and nongovernmental organisations to strategise and prioritise where and how to best extend and implement minimally-invasive life-saving procedures in LMICs. Additionally, these data will facilitate industry growth and partnerships within the unique context of the LMIC setting.

“We believe that increasing the robustness of the ‘WHO Global Atlas of Medical Devices’ will contribute to increasing access to minimally-invasive procedures in LMICs. We want to be actively involved in this process to support the efforts of the WHO in this matter. For example, as trainees, we can assist with facilitating coordination with consultants and suppliers and lead research efforts in evaluating and guiding implementation. We appreciate your efforts in leading equity in global health and look forward to moving forward in our collective commitment to providing all patients with the care that they need and deserve.”

There is a critical need for improving and updating the ‘WHO Global Atlas of Medical Devices’.

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March 2021 | Issue 81

LINC 2021 coverage

PERIPHERAL

Long-term data show sustained efficacy and safety of paclitaxel devices in femoropopliteal lesions A key theme among the late-breaking trial data presented at LINC 2021 (The Leipzig Interventional Course; 25–29 January, online) was the emergence of long-term data on paclitaxel devices in the femoropopliteal segment. Results out to five years show good efficacy and safety.

THOMAS ZELLER (UNIVERSITY HEART Center Freiburg-Bad Krozingen, Bad Krozingen, Germany) presented five-year outcomes of the IN.PACT Global trial, assessing the IN.PACT Admiral drug-coated balloon (DCB; Medtronic), followed

by Young-Guk Ko (Yonsei University College of Medicine, Seoul, Korea), who announced results from the IN.PACT Global Asian cohort. Also presenting data out to five years, Marianne Brodmann (University of Graz, Graz, Austria) detailed new findings from the ILLUMENATE randomised controlled trials (RCTs) of the Stellarex DCB (Philips). Dierk Scheinert (University of Leipzig, Leipzig, Germany) shared three-and-a-half year data from the EffPac study of the Luminor DCB (iVascular), before Michael Lichtenberg (Karolinen Hospital, Arnsberg, Germany) relayed three-year data from the first-in-human KANSHAS 1 study of the novel Kanshas DCB (Terumo).

“Robust, real-world data”: IN.PACT Global five-year outcomes

Zeller informed LINC viewers that the IN.PACT Global study, “remains the largest and only reported real-world DCB study with independent Clinical Events Committee (CEC) adjudication through five years”. The results demonstrate the sustained efficacy of the IN.PACT Admiral DCB through five years and show evidence of long-term safety.

Zeller noted that patients with complex lesions are usually excluded from randomised controlled trials (RCTs); however, they are reflected in real-world studies. “RCTs and global registries have demonstrated the superiority of DCBs over percutaneous transluminal angioplasty (PTA) for the treatment of peripheral arterial disease (PAD) in real-world patients,” he

remarked, though he added that long-term evidence in complex real-world patients is limited.

The IN.PACT Global study is a real-world, prospective, multicentre, single-arm, independentlyadjudicated femoropopliteal study. A total of 1,416 patients were included across 64 sites in the European Union (EU), Middle-East, Latin America, and Asia.

Zeller reported the five-year freedom from clinicallydriven target lesion revascularisation (CD-TLR) rate was 69.4%. He compared this to the rates at one, two, three and four years: 92.%, 83.3%, 76.9%, and 73.4%, respectively. Considering additional efficacy outcomes, Zeller noted that the rate of CD-TLR was 30.6% and that the rate of any TLR was 31.3%.

The primary safety composite endpoint—freedom from device- and procedure-related deaths out to 30 days, freedom from major target limb amputation within 60 months, and freedom from clinically-driven target vessel revascularisation (CD-TVR) within 60 months—was 67.4% at five years.

In addition, there was a 78.9% rate of freedom from all-cause mortality out to five years, and 96.4% followup was achieved with vital status collection.

IN.PACT Admiral demonstrates “consistent treatment effect” in

IN.PACT Admiral DCB

iVascular Luminor DCB

Kanshas DCB

Stellarex DCB

complex geographic subset

Honing in on the Asian subset of the IN.PACT Global study, Ko revealed that this subgroup showed more complex baseline clinical and lesion characteristics than the global clinical cohort. However, he also informed the audience that the Asian subset showed a consistently lower CD-TLR rate of 22.9% at five years for complex femoropopliteal lesions, with a mean length of 17.4±12.4cm and 51.4% total occlusions.

“These results demonstrate a consistent treatment effect with the IN.PACT Admiral DCB across IN.PACT studies, including this complex geographic subset,” he concluded.

Novel approaches and new data for BTK interventions revealed In a late-breaking trial session at LINC 2021 (The Leipzig Interventional Course, 25–29 January, online), key updates on below-the-knee (BTK) interventions were in the spotlight.

F

rancesco Liistro (Azienda Usl Toscana Sud Est, Arezzo, Italy) presented nine-month outcomes from the IN.PACT BTK randomised study. He revealed that the IN.PACT 014 BTK drug-coated balloon (DCB; Medtronic) demonstrates efficacy through nine months compared to

percutaneous transluminal angioplasty (PTA) in a complex population.

The study was a prospective, multicentre, randomised (1:1) feasibility study. Fifty chronic limb-threatening ischaemia (CLTI) patients with infrapopliteal chronic total occlusions (CTOs) were enrolled at nine sites across

Five-year ILLUMENATE outcomes show continued efficacy and safety of Stellarex DCB

Brodmann announced the final, five-year results of two RCTs that show no difference in all-cause mortality between patients treated with the Stellarex DCB and those treated with PTA, the current standard of care. Moreover, the studies showed no difference in mortality between the Stellarex DCB and PTA at every 12-month endpoint over the course of the study.

The ILLUMENATE EU RCT and ILLUMENATE Pivotal RCT together comprised 600 patients in Europe and the USA. After five years, the ILLUMENATE EU RCT showed 19.3% mortality among patients treated with the Stellarex DCB compared to 19.4% mortality for those treated with PTA. The five-year results for the ILLUMENATE Pivotal study also show no statistically significant difference among patients treated with the Stellarex DCB (21.2%) compared to those treated with PTA (20.2%). Both studies had a high vital status follow-up compliance, with the status of over 90% of patients known.

“The five-year final results show favourable overall safety of the Stellarex low-dose paclitaxel DCB, and are applicable within an extensive patient cohort,” said Brodmann. “Every year, the Stellarex programme has demonstrated low mortality rates with no difference in rates between the two patient cohorts.”

Luminor DCB results in “significant haemodynamic improvement” out to 3.5 years in EffPac study

Presenting new findings from the EffPac trial, Scheinert outlined three-and-a-half-year outcomes with the Luminor-35 DCB (iVascular). A total of 166 patients were included in this study; 82 were treated with the Luminor DCB, while 84 were treated with PTA. He concluded that at the 3.5-year timepoint, DCB angioplasty with the Luminor-35 DCB of medium length superficial femoral and popliteal artery lesions results in a, “significant haemodynamic improvement from baseline,” with a lower TLR rate, and an all-cause mortality rate similar to PTA.

Three-year findings of the firstin-human KANSHAS 1 study demonstrates “good safety and efficacy” of novel Kanshas device

Finally, Lichtenberg presented results of the firstin-human KANSHAS study of the novel Kanshas DCB (Terumo), for which there are results for 31 patients. The speaker concluded: “Angioplasty using the novel Kanshas DCB for the treatment of de novo femoropopliteal artery lesions displays good safety and efficacy throughout the period of 36-month follow-up.”

five European countries and followed through 60 months.

Focusing on key eligibility criteria, Liistro told viewers that the “most challenging” lesions were purposefully included in the study, comprising single or multiple total occlusions with lesion lengths ≥40mm.

Sub-segmental late lumen loss was 0.59±0.94 in the IN.PACT 014 DCB group, compared to 1.26±0.81 in the PTA group (p=0.017). He informed viewers that classic late lumen loss was 0.89±0.77 in the DCB group and 1.31±0.72 in the PTA group (p=0.07).

In addition, functional flow by duplex ultrasound (DUS) at nine months was 84.6% in the DCB group and 60.6% in the PTA group (0.341). Finally, he

reported that 91.3% of patients reached the composite safety endpoint.

“This novel, randomised, feasibility study with a 014 BTK balloon utilising the 3.5μg/mm2 drug formulation and enhanced study design provides an opportunity to affect future BTK studies and treatment algorithms.”

ACOART II and ACOART BTK Italy studies support safety and efficacy of Litos DCB Wei Guo (Chinese PLA General Hospital, Beijing, China) presented 24-month results of the multicentre, randomised ACOART II study.

Addressing LINC viewers, Guo

Continued on page 9

Issue 81 | March 2021 described ACOART II as the first randomised BTK trial in China, and— following on from ACOART I—further demonstrates the safety and efficacy of the Litos DCB (Acotec) for the treatment of BTK artery disease.

Regarding 24-month patency, Guo detailed that the rate of clinically-driven target lesion revascularisation (CDTLR) was 10.3% in the DCB group (6/58) compared to 24.6% in the PTA group (14/57; p=0.042), the rate of wound healing was 90% in the DCB group (27/30) vs. 81.3% in the PTA group (26/32; p=0.342), and the rate of major amputation was 3.4% (2/58) vs. 1.8% (1/57) in the two groups, respectively (p=0.565).

Presenting 12-month results of the ACOART BTK Italy study, Liistro noted their similarity to those of the ACOART II study, and concluded that the Litos DCB “shows efficacy and safety in the treatment of complex BTK lesions in CLTI patients”.

“The strongest message for clinicians is the drastic reduction of reocclusion showed by the DCB in baseline occluded vessels,” he informed LINC viewers, adding that future studies should include only occluded vessels at baseline and that the primary endpoint of these studies should be reocclusion

by DUS.

Luminor DCB yields “excellent” results out to 12

LINC 2021 coverage

months

Also to present in the late-breaking session was Tjun Tang (Singapore General Hospital, Singapore), who outlined 12-month outcomes from the MERLION trial of the Luminor DCB (iVascular) in BTK lesions.

The MERLION trial assessed the treatment of long tibial occlusive lesions (TASC C and D) in CLTI patients, the presenter relayed. A total of 50 patients—94% with diabetes, 50% with end-stage renal failure, and 88% with a Rutherford score of either five or six—were included in the study. The cohort had a total of 66 atherosclerotic lesions with a mean lesion length of 13.7±9.5cm.

Tang reported a 100% technical success rate in conjunction with a low rate of bailout stenting (4.5%).

Treatment with the Luminor DCB yielded “excellent” results, he stated, including no deaths within 30 days, and a 12-month amputation-free survival rate of 74%.

In addition, the Luminor DCB proved to be efficacious out to 12 months, with a 69% rate of target lesion primary patency and a 12-month freedom from TLR rate of 82%.

Finally, Tang communicated that wound closure was achieved in 66% of patients and that 60% of patients had improved by at least one Rutherford category at 12 months.

Use of limus-based devices highlighted in four latebreaking trials

Presenting results of the multicentre, dual-blinded, phase II, randomised controlled TANGO study, Ehrin Armstrong (University of Colorado, Aurora, USA) relayed that temsirolimus adventitial drug delivery has provided “robust outcomes” so far, and that a “sizeable effect” has been seen in more complex lesions with temsirolimus delivery.

Twelve-month results from the prospective, single-centre, physicianinitiated PRESTIGE BTK study were also revealed. The objective of this clinical investigation has been to evaluate safety and performance outcomes of the Selution SLR novel sirolimus-eluting balloon (MedAlliance), for the treatment of long tibial occlusive lesions (TASC C and D) in patients with CLTI. Presenter Tze Tec Chong (Singapore General Hospital, Singapore) announced that the primary patency rate was 78% and the rate of wound healing was 81%. In addition, freedom from target lesion revascularisation (TLR) was exhibited by 93% of patients and 84% demonstrated amputation free survival (AFS). All these figures have been sustained from the six-month data.

“We have observed minimal slowflow phenomena and some cases of fast

Study: Patients with depression less likely to go home after critical limb revascularisation A recent analysis by finds an association between depression and non-home discharge after revascularisation for chronic limb-threatening ischaemia (CLTI). Authors Joel L Ramirez, James C Iannuzzi (University of California, San Francisco, USA) and colleagues write in an online Journal of Vascular Surgery (JVS) article that these results “provide further evidence of the negative impact that comorbid depression has on patients undergoing revascularisation for CLTI,” and propose that future studies should examine whether treating depression can improve outcomes in this patient population.

“RECENT EVIDENCE SUGGESTS that depression in patients with peripheral arterial disease (PAD) is associated with increased postoperative complications,” the authors begin, noting that problems can include decreased primary and secondary patency after revascularisation and increased risk of major amputation and mortality.

Ramirez et al note that the impact of depression on non-home discharge after vascular surgery remains unexplored, despite this being “an important outcome” for patients. They hypothesised that depression would be associated with an increased risk for non-home discharge following revascularisation for CLTI. The investigators identified endovascular, open, and hybrid cases of revascularisation for CLTI from the 2012–2014 National (Nationwide) Inpatient Sample, which they explain is “a patient-level administrative claims database that is published annually by the Agency for Healthcare Research and Quality and represents approximately 20% of discharges from US hospitals”.

They write that a hierarchical multivariable binary logistic regression controlling for

hospital-level variation examined the association between depression and non-home discharge and controlled for confounders meeting p<0.01 on bivariate analysis.

Ramirez and colleagues identified 64,817 cases, of which 5,472 (8.4%) were diagnosed with depression, and 16,524 (25.5%) required non-home discharge.

They relay that patients with depression were younger,

These results provide further evidence that an increased awareness about mental health is fundamental to care for vascular surgery patients and to understand postoperative pathways.”

9

wound healing with SELUTION SLR. It is also easy to track and deliver. We are looking forward to gaining further clinical experience with this device,” commented Chong.

Marianne Brodmann (University of Graz, Graz, Austria) revealed results of the DEEPER LIMUS study—a pilot study examining the performance and safety of the limus-coated Temporary Spur stent system (Reflow Medical), which is for clinical investigational use only, in infrapopliteal arteries.

Brodmann stressed that the Temporary Spur stent system provides localised drug delivery, and may prevent acute vessel recoil and increase luminal gain. In addition, she relayed that the system reduced dissection risk through controlled penetration of the vessel wall, and leaves nothing behind, preserving the natural function of the vessel and allowing future treatment options.

The presenter summarised that there were now “promising” clinical data on the Temporary Spur stent system, not only from DEEPER LIMUS, but also from the DEEPER OUS and DEEPER studies.

Reporting outcomes from the multicentre, single-arm DEEPER OUS trial of the Temporary Spur stent system in conjunction with a commercially available paclitaxel-coated balloon, Michael Lichtenberg (Karolinen Hospital, Arnsberg, Germany) echoed the findings presented by Brodmann.

more likely to be women, white, have multiple comorbidities, a non-elective admission, and experience a postoperative complication (p<0.05).

The authors report that, on unadjusted analyses, patients with depression had a 7% absolute increased risk James C Iannuzzi of requiring non-hospital discharge (32.1% vs. 24.9%, p<0.001). On multivariable analysis, they found that patients with depression had an adjusted 50% increased odds for non-hospital discharge (odds ratio [OR]=1.5; 95% confidence interval [CI]=1.4–1.61; c-statistic, 0.81) compared to those without depression.

After stratification by operative approach, Ramirez et al identified that depression had a larger effect estimate in endovascular revascularisation (OR=1.57; CI=1.42–1.74) compared to open (OR=1.45; 95% CI=1.3–1.62).

Finally, the authors write in JVS that a test for interaction between depression and gender showed that men with depression had higher odds of non-hospital discharge compared to women with depression (OR=1.68; 95% CI=1.51–1.88 vs.

OR=1.37; 95% CI=1.25–1.51; interaction p<0.01).

Ramirez and colleagues recognise that the use of a large national administrative database “may introduce bias”.

The authors summarise that this study found a novel association between depression and nonhospital discharge after revascularisation for CLTI. They write: “These results provide further evidence that an increased awareness about mental health is fundamental to care for vascular surgery patients and to understand postoperative pathways.”

March 2021 | Issue 81 CX highlights

10 Section Name

CX to host global discussion of “vital” paclitaxel controversy Andrew Holden (Auckland City Hospital; University of Auckland, Auckland, New Zealand) speaks to Interventional News ahead of this year’s Charing Cross Symposium (CX), which is being held online 19–22 April. In 2021, the conference will focus on controversies within the vascular and endovascular space.

What can delegates expect from this year’s meeting in terms of understanding the paclitaxel controversy?

This year, we are focusing on controversies. While 2020 was clearly the year of the pandemic, those of us who are endovascular specialists remember 2019 as being the year of the paclitaxel controversy, provoked by a meta-analysis that was published just a month or so before the start of 2019 [in the Journal of the American Heart Association (JAHA) by Konstantinos Katsanos (University of Patras, Patras, Greece) et al].

While it is very import to take reports on safety very seriously, many of us were concerned for patients who, subsequent to this meta-analysis, were not receiving some of the profound benefits of paclitaxel-based anti-restenotic therapies in the lower limb arteries, drug-coated balloons and drug-eluting stents. Clearly, these paclitaxel eluting devices have shown superior

patency with lower reintervention rates compared to standard treatment, sustained for many years. Because of that controversy, the use of these devices significantly decreased and there has been real interest in trying to assess if the paclitaxel safety issue was real or due to some other factors, such as trial design, trial patient

We need to think about how we integrate paclitaxel into our current practice, and how the regulators in particular deal with this issue.”

Vascular Access session at CX 2021 to feature conference’s first ever Masterclass on high flow fistulas Nick Inston (University Hospital Birmingham NHS Trust, Birmingham, UK) talks through the highlights of the Vascular Access session at the 2021 Charing Cross (CX) Symposium (19–22 April, online). “I think it is imperative that people keep up their education during this pandemic,” he says. “The way that we work and the way that patient care is delivered have been hugely disrupted and there are definitely things that we can learn from the last year.”

Could you outline the Vascular Access highlights from the programme you have put together for CX 2021?

The CX 2021 Vascular Access programme as usual covers a lot of ground, but there are some real highlights this year. We are going to start the day by talking about devicecreated fistulas, and of course we now have the options of surgically-created or device-created fistulas. Where we use these, how we use these, and what are the expected outcomes will be discussed.

We are also going to delve into the field of high flow fistulas. This is an area that

I think it is imperative that people keep up their education during this pandemic.”

has not really been discussed very much in the past and I think this will be the first Masterclass where high flow fistulas will be in the spotlight. New devices and new evidence are emerging; which balloons are best in vascular access, which stents, where and when should they be used? We will explore all of this.

Why should physicians attend the CX 2021 Vascular Access sessions and what do you think they might learn?

I think it is imperative that people keep up their education during this pandemic.

The way that we work and the way that patient care is delivered have been hugely disrupted and there are definitely things that we can learn from the last year. With these changes in practice it is important to find out what has actually happened to those patients that have not been able to have treatment, or their treatment has been altered. We need to make sure that we learn lessons from each other about new and different approaches to vascular access care.

numbers, and length of follow-up. With that in mind, there has been a huge effort to re-evaluate the data in terms of randomised controlled trials and real-world data, and I am delighted to say that a new meta-analysis with updated five-year data, sheds new light on the paclitaxel mortality issue.

If the paclitaxel mortality issue proves to be incorrect, we need to think about how we integrate paclitaxel into our current practice, and how the regulators in particular deal with this issue. This is important for the global vascular community, because paclitaxel-based products are such a vital component of offering state-of-the-art care for our lowerlimb arterial occlusive patients.

I really look forward to joining you in the controversies sections at Charing Cross 2021.

Andrew Holden

Regional variation in PAD not explained by population differences, CX hear Clinical lead of the National Diabetic Foot Ulcer Audit of England and Wales William Jeffcoate (Nottingham University Hospitals Trust, Nottingham, UK) discusses his presentation on regional variation in peripheral arterial disease (PAD) at the 2021 Charing Cross Symposium (CX; 19–22 April, online) with Interventional News.

Can you briefly summarise the highlights of your own planned presentation for CX 2021?

We are trying to look at the reasons why there is such an enormous regional variation in the incidence of amputation, certainly throughout England and Wales, but also in other countries such as the USA. To do that, we have used the data from the National Diabetes Foot Care Audit of England and Wales—data on slightly more than 26,000 people with diabetes and foot ulcers. We have looked at the different variables that we know are associated with increased risk of major amputation, such as peripheral arterial disease (PAD), age, renal function, etc. and have tried to determine in this very large population how much the variation in the incidence of major amputation across England and Wales can be attributed to population differences. The answer is not very much: not nearly as much as we might expect.

Why is your topic a particularly important one for the global vascular community and why should physicians attend?

This question is important for the global vascular community because it is not a problem that is confined to the UK. In fact, it has been reported from many different countries, and certainly differences in the instance of major amputation in the USA are very similar across the country. So it is of importance to the global vascular community because I think the problem exists globally. There are obviously some parts of the world where there are known factors, such as ethnic differences regarding susceptibilities to PAD, and there are other parts of the world where poverty or social deprivation of one form or another is dominant and that contributes. However, it is important for us to look also at the structure of the provision of care in our own countries and to see how much that might also be contributing to the variation that exists.

What more needs to be done to reduce the levels of major amputation in those with diabetic foot ulcers?

We need to identify the extent of variation in incidence of major amputation that exists in our own country. We then need to determine the extent to which this variation might be explained by differences in the structure and accessibility of clinical care.

Renal

Interventions Positive firsttime data presented at LINC for IN.PACT AV DCB and Ellipsys system New data presented for the first time at LINC 2021 (The Leipzig Interventional Course; 25–29 January, online) support the use of drug-coated balloons (DCBs) as a treatment for dysfunctional arteriovenous fistulas (AVFs). The audience also heard the case for percutaneously-created AVFs with the Ellipsys vascular access system (Medtronic).

ONE-YEAR RESULTS FROM the IN.PACT AV Access study demonstrate superior target lesion primary patency outcomes for DCB angioplasty compared to percutaneous transluminal angioplasty (PTA) for the treatment of de novo or restenotic obstructive lesions of native AVFs in the upper extremity. So said Andrew Holden (Auckland Hospital, Auckland, New Zealand), addressing attendees virtually.

In a comparison of surgical and percutaneous AVF creation, Robert Shahverdyan (Asklepios Clinic Barmbek, Hamburg, Germany) told LINC 2021 attendees that whilst surgically-created AVFs have a higher primary patency and fewer reinterventions, fistulas created by percutenous means with the Ellipsys vascular access system have a higher technical success rate, faster procedure times, higher assisted secondary patency and maturation rates, faster cannulation times, and fewer abandonments.

Superior target lesion primary patency at 12 months with the IN.PACT AV DCB versus standard angioplasty, new data show

In addition to Holden, Robert Lookstein (Ichan School of Medicine at Mount Sinai, New York, USA) and Hiroaki Haruguchi (Haruguchi Vascular Access Clinic, Tokyo, Japan) are principal investigators of the IN.PACT AV Access investigational device exemption (IDE) study, which evaluated the IN.PACT AV DCB (Medtronic) versus PTA. They conducted a global, prospective, 29-centre, 1:1 randomised, singleblinded study evaluating the safety and effectiveness of DCB angioplasty versus PTA in dysfunctional AVF, following 330 patients out to five years.

Each patient enrolled in the study had lesions up to 10cm in length in the native AVF. The primary safety outcome was measured by the serious adverse event rate involving the AVF access within 30 days of the procedure. The primary effectiveness outcome was defined as freedom from clinically-driven target lesion revascularisation (CD-TLR) or access circuit thrombosis, measured through six months post-procedure.

One year after intervention, target lesion primary patency was 65.3% in the DCB group, and 46.3% in the standard PTA group (p<0.001). Access circuit primary patency was also higher amongst the IN.PACT AV DCB cohort: 55.1% versus 35% (p<0.001).

The subset outcomes of the IN.PACT AV Access trial through 12-months were presented for the first time.

Assessing the 12-month data by lesion type, Holden informed the virtual LINC audience that the IN.PACT AV DCB arm demonstrated superior patency in both de novo and restenotic lesions compared to the standard PTA arm. Target lesion primary patency was achieved in 77.5% of de novo lesions treated with the IN.PACT AV DCB (31 of 40), compared to in 61.9% of de novo lesions treated with standard PTA (26 of 42); confidence interval (CI), -4–35.2%. In restenotic lesions, target lesion primary patency was also higher in the DCB group than the standard angioplasty one: 58.4% (59 of 101) versus 35.7% (35 of 98); CI, 9.2–36.2% Looking at the data by of AVF type, the IN.PACT AV DCB group achieved better target lesion primary patency at 12-months for all subgroups: radiocephalic (64.5% vs. 47.2%; CI, 1.5–33%), brachiocephalic (63.8% vs. 41.2%; CI, 3.4–41.9%), and brachiobasilic (61.5% vs. 45.4%; CI,

-23.5–55.6%). Commenting on these results, Holden told delegates: “Fewer reinterventions are needed to maintain target lesion primary patency in the DCB group compared to the PTA group. We saw a 56% reduction in reinterventions at six months, and a 35.4% reduction in reinterventions at 12 months.

“Through 12 months, sustained superior target lesion primary patency was achieved with DCBs in restenotic lesions, and both forearm and upper arm AVF types. Subset analysis of lesion location showed a patency advantage for IN.PACT AV DCB over standard PTA for all lesion locations in the access circuit but particularly at the arterial inflow, anastomosis and cephalic arch.”

Through 12 months, sustained superior target lesion primary patency was achieved with [the IN.PACT AV] DCB in restenotic lesions – Andrew Holden

Percutaneous AVF creation with Ellipsys faster, and “easier to salvage” than surgically-created AVFs

In a comparison of surgical and percutaneous AVF creation, Shahverdyan told LINC 2021 attendees that whilst surgical AVFs have a higher primary patency and fewer reinterventions, percutaneous AVFs with the Ellipsys vascular access system (Medtronic) have a higher technical

success rate, faster procedure times, higher assisted secondary patency and maturation rates, faster cannulation times, and fewer abandonments.

There are currently two systems available on the market that allow for AVFs to be created percutaneously: the Ellipsys vascular access system and the WavelinQ 4F endoAVF system from BD. Comparing these two endovascular AVF options with the surgical Gracz technique, the investigators created over 500 new vascular accesses during the study period in total, from which Ellipsys was used in 116 patients, WavelinQ 4F in 41 patients, and Gracz surgical AVF creation was performed in 90 patients.

Technical success was 100% in the Ellipsys and surgical Gracz groups, and 92.7% in the WavelinQ group.

The procedure time was significantly shorter when using the Ellipsys, 13 minutes versus over an hour in the WavelinQ and Gracz arms.

Shahverdyan shared that maturation at four weeks “is similarly high for Ellipsys and Gracz” (78.4% and 80%, respectively), and that they observed total maturation in 88% of patients for both these groups. Time to cannulation in dialysis patients was shorter for Ellipsys procedures (52 days vs. 69 days in the surgical cohort), and, although there were more interventions in the endoAVF groups, fewer Ellipsys AVFs were abandoned or converted to another fistula (12.3% vs. 36.6% in the WavelinQ group and 15.6% in the surgical group).

At six months, one year, and two years, primary patency was highest in the surgical Gracz group (68%, 53%, and 42%, respectively). The Ellipsys had the second highest primary patency at all time points (50%, 34%, and 27%, respectively), whilst primary patency with WavelinQ was lowest (35%, 27%, and 23%, respectively). However, assisted patency rates at six months, one year, and two years were similarly high for Ellipsys (83%, 77%, and 77%, respectively) and Gracz (84%, 80%, and 78%, respectively) groups.

“To conclude,” Shahverdyan said, “Ellipsys demonstrates high technical success and faster procedural times compared with both surgical and WavelinQ procedures. It shows similarly high assisted and secondary patency and maturation rates as the Gracz fistula, and [...] shows significantly higher secondary patency rates.”

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Renal

April 2021

Interventions Network meta-analysis finds DCB angioplasty “significantly superior” to plain balloon angioplasty in failing AVFs withoutflow stenosis A recent network meta-analysis shows that, in failing arteriovenous fistulas (AVFs) with outflow stenosis, drugcoated balloon (DCB) angioplasty is “significantly superior” to plain balloon angioplasty, presenting an improved six-month failure rate. However, Gregory Tripsianis (Democritus University, Alexandroupolis, Greece) and colleagues stress that the effectiveness of DCB angioplasty in the long term “deserves further investigation”.

WHILE THE 2018 EUROPEAN Society for Vascular Surgery (ESVS) vascular access clinical practice guidelines recommend balloon angioplasty for the treatment of venous outflow stenosis to extend the use of AVFs, the authors note that its effectiveness compared to other endovascular modalities “remains unclear”. In fact, they state more generally that “there is currently uncertainty regarding the ideal treatment to salvage failing AVFs”.

Writing in an online Journal of Vascular Surgery (JVS) article, Tripsianis et al note that it was their intention in this study to investigate the comparative effectiveness of the different endovascular treatments in patients with failing autogenous AVFs with outflow vein stenosis.

The investigators detail that they searched Medline/PubMed and SCOPUS databases for studies that fit the criteria of being randomised controlled trials (RCTs), compared endovascular treatments of autogenous AVF stenosis—including plain balloon angioplasty, cutting balloon angioplasty, and DCB angioplasty— and provided six-month and/or oneyear patency data for each group at follow-up.

Inclusion criteria were venous outflow, anastomotic or swing area stenosis, either de novo or recurrent, and exclusion criteria were central vein stenosis or RCTs including open surgical repair or stent/stent graft arms.

Following the literature search, Tripsianis and colleagues performed a systematic review and network meta-analysis of RCTs investigating

the effectiveness of plain balloon angioplasty, cutting balloon angioplasty, and DCB angioplasty in autogenous AVFs vein stenosis. They write that they included eleven RCTS in the study, reporting a total of 814 patients, of whom 395 underwent plain balloon angioplasty.

According to the authors, their network meta-analysis showed that DCB angioplasty at six months was “significantly more effective” than plain balloon angioplasty (odds ratio [OR]: 0.39, confidence intervals [CI]: 0.18–0.81) and ranked as the best treatment option, but without having statistically significant difference when compared with cutting balloon angioplasty (OR: 0.65, CI: 0.2–2.12).

Writing in JVS, the investigators also report that statistical significance was not achieved at one year among treatments, and that additional conventional pair-wise meta-analyses did not find significant differences at one year.

There is currently uncertainty regarding the ideal treatment to salvage failing AVFs.” Tripsianis et al stress that the results of this review “should be interpreted with caution” due to some limitations.

Firstly, they acknowledge that the

Senior authors Miltos Lazarides (left) and George Georgiadis (right)

network geometry did not provide any closed loops and write that “no direct comparison between DCB angioplasty and cutting balloon angioplasty existed, thus it was impossible to assess inconsistency between direct and indirect evidence”.

In addition, they note that there was “a considerable degree of heterogeneity” among the included RCTs and that confounding factors were present. They detail: “There was blending of various AVF configurations, de novo lesions with

and difference in methodology of angioplasty regarding predilatation or post-dilatation following DCB angioplasty”.

Finally, they recognise that there was “a high risk of bias” among the included studies, especially those comparing plain balloon angioplasty with cutting balloon angioplasty.

Tripsianis et al detail that most of the trials suffered from the “inherently high risk in the domain of blinding,” specifying that all but one of the included studies suffered from bias

COVID-related hypercoagulability linked to elevated malfunction rate in temporary haemodialysis catheters Hypercoagulability in COVID-19 patients leads to an increase in the malfunction rate of temporary haemodialysis catheters—but heparin locking of the catheters is linked to decreased malfunction rates, a new study finds.

John J Kanitra (Ascension St John Hospital, Detroit, USA) and colleagues carried out a retrospective cohort study via chart review at their institution—a large urban hospital. Writing in the Journal of Vascular Surgery, they report that a total of 48 patients with a mortality rate of 71% were identified. Malfunction occurred in 31.3% of patients. Thirty-seven patients (77.1%) received heparin locking, 22 (45.8%) received systemic anticoagulation and 38 (79.1%) received venous thromboembolism prophylaxis. The overall rate of malfunction was lower at a trend level of significance with heparin versus saline locking (24.3% vs. 54.6%; p=0.058), Kanitra et al found. Meanwhile, systemic anticoagulation did not affect temporary catheter malfunction rate (p=0.240). Higher D-dimer levels were related to greater mortality (hazard ratio [HR] 3.28, 95% confidence interval [CI] 1.16–9.28; p=0.025), but were not significantly associated with temporary catheter malfunction (HR 1.79, 95% CI 0.42–7.71; p=0.434). recurrent ones, high-pressure balloon use in a variable number, different brands of DCBs and paclitaxel dose, differences in patency reports (target lesion versus circuit patency),

in blinding or personnel, as this is “almost impossible” in endovascular procedures. However, they note that there was some blinding of the outcome assessment in six studies.

April 2021

Arterial diameter may help to predict AVF aneurysm progression, study suggests A recent study concludes that arterial diameter may influence arteriovenous fistula (AVF) aneurysm progression and the interval to surgical revision. “Patients with larger arterial diameters should be monitored closely and referred early after aneurysm development,” authors Alexis M Cahalane (Massachusetts General Hospital, Boston, USA) and colleagues write in an online article in The Journal of Vascular Access (JVA).

ANOTHER KEY FINDING FROM the study was that radiocephalic AVFs are more resistant to aneurysm development, and “should be considered the first access option for ESRD [end stage renal disease] patients, especially younger patients,”

the authors communicate.

This study included all patients who underwent fistula surgical revisions due to aneurysms between 1 January 2014 and 30 July 2016. From this data pool, the investigators collected patients’ demographics and AVF dimensions based on fistulograms.

They identified a control group with non-aneurysmal AVFs who had undergone serial fistulograms between 2013 and 2016.

In this retrospective study, Cahalane et al identified 45 eligible patients in the AVF aneurysm group and 24 in the control group, with the mean age of AVF creation being older in the control group (61.8 vs. 53 years, p=0.03).

Writing in JVA, they report that the mean interval between AVF creation and first fistulogram in the study group was 1,464±282 days, compared to an interval of 263±101 days in the control group (p=0.003). Cahalane et al added that the arterial diameter on first fistulogram (r=0.6, p=0.03) predicted maximum aneurysm diameter on the last fistulogram (r=0.6, p=0.03) as well as the interval between first fistulogram and surgical revision (r=0.33, p=0.03).

In the discussion of their findings, the authors note that the study group contains only a small number of patients with heterogeneous distribution of AVFs.

New standardised reporting system suggests arteriovenous graft infections may be less frequent than previously described “Using an objective system that discriminates between aetiology and outcome allows a more complete, objective understanding of relative infection risks and outcomes for arteriovenous grafts (AVGs).” This is the conclusion of a review published online in The Journal of Vascular Access (JVA). Authors David Kingsmore (Queen Elizabeth University Hospital, Glasgow, UK) and colleagues suggest that such a system can inform discussions with patients requiring vascular access for haemodialysis.

THE AUTHORS FOUND THAT AVG INFECTION WAS NOT COMMON, that it was caused by a systemic infection in only one-third of patients, did not lead to metastatic infection, and, “importantly,” was treatable without loss of access in one-half of all cases.

“The perception that AVG infection is frequent and severe is not based on contemporary data from large units using modern AVGs,” the authors state. Furthermore, they write that older reports “compounded misperceptions” by using non-standardised reporting that prevents easy comparison against the alternative modalities.

In their review, Kingsmore et al used a recently-published reporting scheme to analyse the frequency, management, and outcome of AVG infection in a large series of sequential early-cannulation AVGs with longterm follow-up. The aim was to assess the application and implications of a standardised reporting system for AVG infection. They performed a single-centre series analysis of 277 early-cannulation AVGs with a minimum of one-year follow-up.

VasQ external support awarded NUB Status 1 reimbursement renewal for 2021 for 321 hospitals The German Institute for Hospital Remuneration (InEK) has renewed the new examination and treatment methods (NUB) Status 1 designation of VasQ external support (Laminate Medical Technologies) for 2021.

NUB STATUS 1 PROVIDES SUPPLEMENTAL reimbursement for innovative medical devices that have the potential to improve the standard of care for patients. VasQ external support first received NUB Status 1 in 2017 with 35 participating hospitals and has since grown to 321 participating hospitals to date, which represents the second most among devices that serve the dialysis patient population.

The VasQ external support is implanted around the anastomosis during the creation of an arteriovenous fistula (AVF) to promote more usability without the need for the frequent additional procedures typically required for standard AVFs. AVFs created with the VasQ external support have reported in publications and presentations usability rates as high as 86% or better by six months in seven clinical studies. Growing clinical evidence in support of VasQ as well as the building momentum of usage in InEK calculating hospitals are critical components to support a permanent diagnosis-related group (DRG) code for reimbursement.

“My practice relies on VasQ as our standard of

care for creating almost all of our forearm and upper arm surgical fistulas,” stated Robert Shahverdyan, head of Vascular Access Center Hamburg at Asklepios Klinik Barmbek (Hamburg, Germany).

“The device has improved my fistula outcomes for my patients, and I am grateful for the NUB designation so my work with VasQ can continue with sufficient reimbursement to cover the additional costs of the device.”

The device is currently being implanted across Europe under a CE mark and has also completed enrolment in an investigational device exemption (IDE) pivotal clinical study to be evaluated by the US Food and Drug Administration (FDA) through the de novo pathway for use in the USA. The FDA has already awarded the device a breakthrough designation based on the breadth of clinical evidence collected so far for VasQ that consistently demonstrates improvement over the standard of care for AVF creation. The designation provides VasQ with the substantiation of clinical improvement required by the Centers for Medicare

and Medicaid Services (CMS) for providing additional reimbursement for new technologies once cleared for the US market.

VasQ device improves AVF creation in haemodialysis patients

VasQ could be protective against the haemodynamic modifications that occur during arteriovenous fistulae (AVF) creation, a recent article in The Journal of Vascular Access reports. Roberto Palumbo (Saint Eugenio Hospital, Rome, Italy) and co-authors caution that their results, which derive from their clinical experience and are thus representative of a “real-life setting”, should be considered preliminary.

The designation provides VasQ with the substantiation of clinical improvement required by the CMS for providing additional reimbursement for new technologies once cleared for the US market.”

13

March 2021 | Issue 81

14 Peripheral interventions

LINC 2021

Head-to-head trials take centre stage in drug-eluting technology latebreaking session at LINC Data from two head-to-head trials on drug-eluting technologies in femoral artery treatment were presented during a late-breaking session at LINC 2021 (The Leipzig Interventional Course; 25–29 January, online)—one-year TRANSCEND and two-year COMPARE results. Both studies point to the non-inferiority of lowerdose paclitaxel devices, prompting discussion on whether these results will see a trend towards using lower-dose devices in practice. Although these results are promising, the panel agreed that more data are needed.

KENNETH ROSENFIELD (MASSACHUSETTS General Hospital, Boston, USA) presented one-year results of the TRANSCEND study, a non-inferiority randomised trial comparing the efficacy and safety of the SurVeil drug-coated balloon (DCB; Surmodics) versus the IN.PACT Admiral DCB (Medtronic), and Sabine Steiner (University of Leipzig, Leipzig, Germany) presented two-year results from the COMPARE trial, assessing the Ranger DCB (Boston Scientific) compared to the IN.PACT device.

All DCBs assessed utilise the anti-proliferative drug paclitaxel. The SurVeil and Ranger DCBs both have a low dose of paclitaxel (2µg/mm²) compared the the IN.PACT Admiral DCB, which has a higher dose of 3.5μg/mm².

TRANSCEND one-year results: SurVeil demonstrates non-inferior efficacy and safety versus IN.PACT Admiral

Rosenfield announced that primary results of TRANSCEND demonstrate the non-inferiority of the SurVeil DCB compared to the IN.PACT Admiral DCB with regards to both safety and efficacy, while delivering a substantially lower drug dose.

In the TRANSCEND trial, the SurVeil DCB was found to be non-inferior to the IN.PACT Admiral DCB in both the primary safety and primary efficacy endpoints. The SurVeil DCB cohort (n=222) exhibited a strong safety profile with 91.7% of subjects demonstrating freedom from device- or procedurerelated death within 30 days and freedom from above-ankle amputation or clinically-driven target vessel revascularisation (CD-TVR) within 12 months, compared to 89.6% of subjects treated with the IN.PACT Admiral DCB (n=224).

The SurVeil DCB group also met its efficacy endpoint of primary patency of 81.7% as compared to 85.9% of the IN.PACT Admiral DCB arm. In addition, the number of reinterventions deemed clinically necessary by physicians did not differ between the products.

COMPARE two-year results: Ranger continues to demonstrate similar patency rate to IN.PACT

Two-year results from COMPARE, the first head-tohead comparison of two DCBs with different paclitaxel dosages and coating technologies for femoropopliteal interventions, were also presented.

The study compared the lower paclitaxel dose Ranger DCB to the higher paclitaxel dose IN.PACT Admiral DCB. One-year results of COMPARE were presented for the first time during LINC 2020 (Leipzig Interventional Course; 28–31 January, Leipzig, Germany) and published concomitantly in the European Heart Journal.

At two years, the Ranger DCB, which has a significantly lower drug dose density of paclitaxel, continued to demonstrate a similar primary patency rate to the higher-dose IN.PACT DCB with a freedom

restenosis rate of 70.6% for the Ranger DCB (n=207) compared to the 71.4% observed with the IN.PACT DCB (n=207), according to a Kaplan-Meier estimate (p=0.96).

No significant differences were observed for other Kenneth Rosenfield secondary two-year outcomes, Steiner informed the LINC audience, detailing low all-cause mortality rates at twoyears with 3.6% for the Ranger DCB vs. 2.2% for the IN.PACT DCB (log-rank p=0.6).

In addition, there was a low clinically-driven target lesion revascularisation (CD-TLR) rate through two years—17.8% for the Ranger DCB vs. 13% for the IN.PACT DCB (p=0.3).

versus a high-dose balloon was also evident.

Both TRANSCEND and COMPARE assessed low-dose devices to the high-dose IN.PACT Admiral DCB. In the same late-breaking session, Thomas Zeller (University Heart Center Freiburg-Bad Krozingen, Bad Krozingen, Germany) had presented long-term data on this device. Scheinert asked for his opinion on the results.

“We have to wait for longer-term follow-up data in order to see whether there will be a difference in terms of future safety endpoints,” Zeller remarked.

“However, it is interesting to see that all the data with the first-generation DCB [IN.PACT Admiral] are more or less in line, independently of whether the maker of this device has conducted the trial, or if this balloon was used as a control,” he added, highlighting the strong data available for the device.

In terms of whether this should herald a move towards low-dose devices, Zeller was unconvinced: “I do not see a reason to switch, and I do not know whether it is really necessary.”

Panellist Marianne Brodmann Sabine Steiner (University of Graz, Graz, Austria) also commented, echoing Rosenfield: “If a low-dose device is as safe and as efficient in the long term as a high-dose device, I think a lot of physicians might feel more comfortable to use a low-dose device.” However, she also stressed that more data on these low-dose devices are needed.

Results for low-dose devices “reassuring,” but more data needed

Subsequent discussion focused on the significance of these results, with moderator Dierk Scheinert (University of Leipzig, Leipzig, Germany) posing the question: “Are low-dose balloons the way to go in the future?”

Rosenfield responded: “I think that this new generation of balloons is going to be better, and the safety data are comparable. If you are going to use multiple balloons in a given patient, I would certainly feel a lot more comfortable using a lower-dose balloon with better transmission of the drug and with less particulates downstream. I believe that this is going to be the way to go. Also, the technology is constantly improving.”

We have to wait for longer-term followup data in order to see whether there will be a difference in terms of future safety endpoints – Thomas Zeller, panellist

Steiner was in agreement, noting that the results are “reassuring”. While the data from both TRANSCEND and COMPARE point in a similar direction, Scheinert was curious to know if there are any key differences between the datasets. “COMPARE included longer lesions, up to 30cm,” Steiner began, adding that it also included more chronic total occlusions (≈40% CTOs).

However, the speaker noted this design came at a price, referring to a much higher bailout stenting rate than TRANSCEND. Steiner also remarked that with the “more typical” design of TRANSCEND, with lesions of up to 18cm only, non-inferiority for a low-dose

2µg/mm² 2µg/mm² The SurVeil and Ranger DCBs both have a low dose of paclitaxel (2µg/ mm²) compared the IN.PACT Admiral DCB, which has a higher dose of 3.5μg/mm²

3.5µg/mm²

March 2021 | Issue 81

16 Peripheral interventions

Acute kidney injury is associated with medium-term mortality following endovascular intervention for PAD Acute kidney injury is a common complication after intervention for peripheral arterial disease (PAD), and is associated with “medium-term mortality” following percutaneous transluminal angioplasty (PTA), a new study in the British Journal of Surgery (BJS) finds. Authored by Emmanuel Katsogridakis (National Institute for Health Research, Leicester Biomedical Research Centre, University of Leicester, Leicester, UK) and colleagues, the paper concludes that while the present work makes evident the fact that the development of acute kidney injury is independently associated with medium-term mortality at two years, the observational nature of the study means the authors “cannot fully elucidate the pathophysiological mechanisms underlying this association”. They call for future research using relevant subclinical markers and mechanistic assessments to shed light on this.

SYMPTOMATIC PAD IS FREQUENTLY managed with PTA, particularly in patients with significant comorbidities, including chronic kidney disease (CKD) and cardiovascular disease. These patients are at risk of developing acute kidney injury after PTA. Postprocedural AKI is not innocuous, the authors write, even for patients with a transient decline in renal function, as it is strongly associated with more complications and a higher financial burden for healthcare providers. As the incidence of, and risk factors for, acute kidney injury after endovascular intervention for PAD are unknown, the study investigators sought to assess the proportion of patients who develop acute kidney injury, and to explore the risk factors.

Their primary aim was to assess the incidence of acute kidney injury after PTA. The primary outcome was therefore the proportion of patients who developed acute kidney injury after PTA, using the Kidney Disease Improving Global Outcomes (KDIGO) reporting criteria. Secondary outcomes were the proportion of patients who died, underwent a major amputation, required dialysis within 90 days of intervention, remained dialysis-dependent after 90 days of intervention, or developed the major adverse

kidney events (MAKE) endpoints—death, dialysis, and/or drop in estimated glomerular filtration rate of at least 25%—at 30 or 90 days (MAKE30 and MAKE90, respectively).

Katsogridakis et al prospectively collected and analysed data on 2,041 patients undergoing femoropopliteal endovascular intervention for symptomatic PAD (Rutherford stages III–VI) between 2014 and 2019 across three vascular centres.

Acute kidney injury developed in 239 patients (11.7%), with 47 (2.3%) requiring dialysis within

Efforts in the prevention of this complex and important complication of endovascular therapy, addressing high-risk groups, are a priority.”

Introduction of dedicated vascular limb salvage clinic improves oneyear amputation outcomes for CLTI patients One-year outcomes of patients with chronic-limb threatening ischaemia (CLTI) treated in an outpatient-based vascular limb salvage clinic show an improved rate of major amputation.

Authors Andrew Nickinson (University of Leicester, Leicester, UK) and colleagues write in an online European Journal of Vascular and Endovascular Surgery (EJVES) article that their study supports the recommendations of the Global Vascular Guidelines and “provides a reproducible service model that delivers timely vascular assessment in an ambulatory setting”.

W

hile vascular limb salvage services are recommended by the Global Vascular Guidelines to help improve outcomes for patients with CLTI, the authors write that literature on the topic is limited. It was the aim of this study, therefore, to provide data on the effect of treating CLTI patients in an outpatient-

30 days, and 18 (0.9%) requiring ongoing dialysis.

The MAKE30 and MAKE90 composite endpoints were reached in 358 (17.5%) and 449 (22%) patients respectively. Risk factors for acute kidney injury were age, sex, congestive heart failure, chronic limb-threatening ischaemia, emergency procedure, and pre-existing chronic kidney disease. Acute kidney injury, dementia, congestive heart failure, and major amputation were risk factors for medium-term mortality, the authors report.

Commenting on these findings, Katsogridakis and colleagues note: “The acute kidney injury-specific risk factors identified in this series are mostly nonmodifiable. Older age, male sex, history of congestive heart failure, CLTI [chronic limb-threatening ischaemia], and preoperative renal function have all been associated with acute kidney injury development previously in a variety of clinical settings, and were strongly associated with acute kidney injury in this study. It is not surprising that these parameters are

based vascular limb salvage clinic on amputation outcomes.

The George Davies Research Group, based at the University of Leicester, undertook an analysis of a prospectivelymaintained database, involving all consecutive patients diagnosed with CLTI within the Leicester Vascular Limb Salvage (VaLS) clinic from February

Acute kidney injury developed in 239 patients (11.7%), with 47 (2.3%) requiring dialysis within 30 days, and 18 (0.9%) requiring ongoing dialysis

associated with acute kidney injury in patients with severe PAD. Alongside these findings, the absence of correlation between contrast volume and subsequent acute kidney injury in this series further confirms that acute kidney injury encompasses a plethora of other pathophysiological mechanisms, including perioperative volume depletion, nephrotoxicity, and renal microembolisation. Efforts in the prevention of this complex and important complication of endovascular therapy, addressing high-risk groups (elderly, men, CLTI, CKD, and heart failure), are a priority.”

2018 to February 2019.

They compared data with two comparator cohorts, identified from coding data: 1) patients managed prior to the clinic, between May 2017 and February 2018 (Pre-Clinic [PC]); and 2) patients managed outside of clinic, between February 2018 and February 2019 (Alternative Pathways [AP]).

Freedom from major amputation at 12 months was the primary outcome.

Writing in EJVES, Nickinson et al detail that 566 patients were included (median age 74 years) in the study.

They report that patients managed

It is great to see how interest is building across the UK in improving the outcomes for patients with CLTI.

within the VaLS cohort were statistically significantly more likely to be free from major amputation (90.5%) compared with both the AP (82.1%; adjusted hazard ratio [aHR] 0.52; 95% confidence interval [CI] 0.28–0.98; p=0.041) and the PC (80%; aHR 0.5; 95% CI 0.28–0.91; p=0.022) cohorts at 12 months, after adjustment for age, disease severity, anti-platelets/lipid lowering therapies and presence of diabetes.

Following the publication of these results, Nickinson spoke to Interventional News about their significance: “We are really excited about the publication of these results in the EJVES, the culmination of a great deal of effect by the whole team in Leicester. Our sincere thanks go to George Davies Charitable Trust, whose generous donation has made the VaLS clinic a reality. Looking forward, a number of centres have now setup similar services across the UK and with the ongoing work of the Vascular Society’s PAD Quality Improvement Programme, it is great to see how interest is building across the UK in improving the outcomes for patients with CLTI.”

CONTROVERSIES

CHALLENGES

CONSENSUS

Vascular & Endovascular

Controversies Update

19–22 APRIL 2021 MONDAY-THURSDAY Aortic Controversies

Peripheral Arterial Controversies

Venous & Lymphatic Controversies

Acute Stroke Controversies

Vascular Access Controversies

The Hurting Leg Controversies

DIGITAL EDITION WWW.CXSYMPOSIUM.COM CX 2021 will be streamed live daily with audience participation, discussion and polling

EDUCATION

INNOVATION

EVIDENCE

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1 Covera™ Vascular Covered Stent is being compared to the Gore™ Viabahn™ Endoprosthesis on the basis of that each are indicated for the treatment of stenosis in the venous outflow at the venous anastomosis of a synthetic arteriovenous (AV) graft.

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N=13; COVERA™ Vascular Covered Stent implant size 7x60mm; GORE™ Viabahn™ implant size 7x50mm; Test performed at 1mm oversizing, (0.17 N/mm vs. 0.13 N/mm).

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The Covera™ Vascular Covered Stent is indicated for use in hemodialysis patients for the treatment of stenoses in the venous outflow of an arterio-venous (AV) fistula and at the venous anastomosis of an ePTFE or other synthetic AV graft.Do not use if you have uncorrectable coagulation disorders or are hypersensitive to nickel-titanium or tantalum. Please consult product labels and instructions for use for indications, contraindications, hazards, warnings and precautions.

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Issue 81 | March 2021

Prostate artery embolization 19

Patients with stromal enlargement of the prostate benefit the most from PAE, twoyear STREAM trial data reveal Prostate artery embolization (PAE) is a good treatment option for patients with benign prostatic hyperplasia (BPH) with minimal complications, according to the 24-month results of the STREAM trial, which affirms the place of the minimally invasive procedure in interventional radiologists’ arsenal. This magnetic resonance image (MRI)-based study looked to examine factors important in predicting successful PAE using MRI over a two-year follow-up period. The triallists report that while adenomatous BPH does particularly well in the short term when treated with PAE, stromal BPH demonstrates better results at two years. In addition, they conclude that patients with median lobe hypertrophy (MLH) do as well as those without MLH up to 24 months, and that initial prostate volume does not appear to be significant in predicting outcomes at two years.

“T

symptom score (IPSS), international index of erectile function (IIEF), and validated quality of life (QoL) EQ-5D5L questionnaires.

The technical success rate was 96%— no prostate arteries could be identified intraprocedurally in two of the 50 patients. The study authors report only minor complications arising from PAE: two cases of acute urinary retention and one case of uncomplicated urinary tract infection. While this is positive, the authors state that, “Unfortunately, as there was no comparison group or control group in this study, it is not possible to make direct comparisons between different minimally invasive methods for treating BPH.”

Clinical outcomes

Clinical outcomes of the STREAM trial were also positive. The mean IPSS score dropped from a baseline score of 21.1 (range: 16–36) to 7.2 at 12 months, and 8.1 at 24 months. Meanwhile, results from the EQ-5D-5L quality of life questionnaire demonstrated an increased quality of life at three, 12, and 24 months post-procedure. Results from the IIEF showed no significant change in erectile function over the two-year

his study has provided valuable information and allowed a better understanding of which glands respond and how they will respond to PAE,” Charles Tapping (Churchill Hospital, Oxford, UK) and co-authors write in Cardiovascular and Interventional Radiology (CVIR). “It also allows clinicians to provide more information to patients exploring treatment for their BPH. MLH responded as well as non-MLH BPH disease, suggesting this technique may be valuable in treating patients with MLH, especially if some of the other minimally invasive techniques are limited if significant MLH is present.”

STREAM trial data at two years proves the technical and clinical success of PAE

“PAE has established itself as one of the alternative minimally invasive treatments for BPH, and is now accepted as safe and effective,” Tapping et al write. They go on to say that while performing PAE can be technically challenging, with a significant learning curve to perform the technique successfully, it is important to ascertain factors that may aid in predicting which patients would benefit most from PAE. They note that this is a particular imperative for interventional radiologists as there are “a number of robust minimally invasive techniques to treat BPH, such as the Urolift system and water vapour thermal therapy (REZUM)”.

They therefore conducted a prospective cohort study of 50 patients with BPH who were treated with PAE at a single institution. Patients had moderate to severe symptoms of BPH

Greatest improvement in IPSS score seen in patients with adenomatous BPH

“An interesting analysis of the results showed that while adenomatous BPH had an initial greater reduction in their IPSS score, improvement in quality of life, and symptoms (at three and 12 months compared to stromal group), the stromal group had better results at 24 months,” Tapping and colleagues say.

“In fact”, they write, “there was a continued decline in IPSS score in the stromal group over the 24-month study period, with a slight increase in IPSS score in the adenomatous group from 12 to 24 months.”

While the stromal prostate gland volume decreased compared to baseline size at three, 12, and 24 months postPAE, the adenomatous glands at first rapidly reduced in size, maintained this small volume out to 12 months, and then increased in size again, with a larger volume reported at 24 months.

Discussing this finding, the triallists say: “This adds to the previously perceived literature that suggests adenomatous BPH patients had a better outcome. Angiography of adenomatous masses within the prostate demonstrates that these are highly vascular structures and the more rapid reduction in symptoms and IPSS score can be accounted for by infarction of the adenoma and rapid reduction in pressure on the transition zone of the prostate. Moreover, the more gradual improvement in the stromal group corresponds to typically a less vascular pattern on angiography.”

Patients with median lobe hypertrophy do just as well post-PAE as those without median lobe hypertrophy

This study has provided valuable information and allowed a better understanding of which glands respond and how they will respond to PAE.” PAE may be a good option for patients with median lobe hypertrophy that cannot have alternative minimally invasive forms of treatment for their BPH.” refractory to medical management for at least six months prior to enrolment in STREAM. Patients were imaged with multiparametric MRI imaging pre-PAE, and at three months, 12 months, and 24 months post-procedure. Clinical success was measured with international prostate

study following PAE. The prostate volume as measured on MRI imaging was significantly reduced from baseline to three months post-PAE. There was then a non-significant volume reduction at 12 and 24 months when compared to baseline.

No significant difference in IPSS score was observed at any time point between the 19 patients with MLH and those without MLH, according to the STREAM trial findings.

“Typically,” Tapping and co-authors muse, “it has been considered that patients with MLH would not do as well with PAE. “However, patients in this cohort did as well as those without MLH. PAE may therefore be a good option for patients with MLH that cannot have alternative minimally invasive forms of treatment for their BPH.” There was no significant correlation between initial prostatic volume and the IPSS score at 12 and 24 months post-PAE (p=0.05). While previous investigators have suggested that prostate size is associated with clinical success following PAE, Tapping et al consider that, in their study, MRI provided extra detail of the internal prostate architecture, meaning that “factors such as adenomatous predominant and stromal dominant disease became more useful”.

They call for further studies to overcome the limitation imposed on this trial by its small sample size.

March 2021 | Issue 81

20 The embolization vanguard

Embosphere microspheres comparable to Imipenum Cilastatin microspheres for GAE in patients with knee osteoarthritis

Trisacryl gelatin microspheres 100–300μm in size can be considered for genicular artery embolization (GAE), a new study presented at the 2021 meeting of the Society of Interventional Radiology (SIR; 20–26 March, online) reports. Presenting the two-year outcomes of a study comparing Embosphere microspheres (Merit Medical), which are made of trisacryl gelatin, with Imipenum Cilastatin microspheres for GAE in patients with moderate to severe knee osteoarthritis, Shivank Bhatia (University of Miami Miller School of Medicine, Miami, USA) informed delegates that the particles are comparable in terms of pain reduction, and that there is a sustained effect up to two-years of follow-up.

“GENICULAR ARTERY EMBOLIZATION HAS potential to provide midterm relief of pain for patients with mild-to-moderate knee osteoarthritis resistant to conservative management,” he said.

Detailing their methodology, Bhatia described how the investigators conducted a prospective study, assessing a total of ten patients (15 knees) who had a GAE with 100–300μm Embosphere microsphere particles, and comparing them to a subsequent cohort of eleven patients (18 knees) who underwent GAE with Imipenum Cilastatin microspheres. Clinical outcomes were evaluated at six-month and 24-month follow-up and compared to baseline using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire.

Bhatia noted that, at baseline, there were no

significant differences in sex, age, body mass index (BMI), duration of pain before the procedure, prior treatment, or Kellgren-Lawrence grade between the two cohorts. Baseline median pain WOMAC and total WOMAC scores were 13 (interquartile range [IQR], four) and 46 (IQR, four) in the Embosphere group and 13 (IQR, three) and 47 (IQR, 28) in the Imipenum Cilastatin group [p=0.875 and p=0.738], respectively.

The median follow-up was 796 days (range, 736– 808). Clinical success (measured as 50% reduction in WOMAC pain score vs. baseline) was achieved in 69.23% of the embolized knee joints in both groups (p=1) at six months.

At two-years follow-up, the investigators report clinical success in 61.5% of knees treated with the Embosphere microspheres, versus a 53.8% clinical

PAE practice: A decade in review Shivank Bhatia Vedant Acharya Comment & Analysis Shivank Bhatia and Vedant Acharya highlight the importance of multidisciplinary collaboration between urologists and interventional radiologists when it comes to forming a successful prostate artery embolization (PAE) clinic, citing a decade of experience at the Miami Miller School of Medicine (Miami, USA).

P

rostate artery embolization (PAE), an endovascular treatment for benign prostatic hyperplasia (BPH)related lower urinary tract symptoms (LUTS), was initially performed to control pelvic bleeding of prostatic origin.

It was found that the prostate decreased in size. With this insight, the first use of PAE to intentionally treat BPH-associated LUTS was performed in 2000. Larger case series published in 2010–2011 reproduced these initial findings. The presentation of these results at the Society of Interventional Radiology (SIR) 2011 conference [26–31 March, Chicago, USA] led to increasing international interest in studying the effects of PAE. Over the past 10 years, the PAE landscape has seen a tremendous explosion of research interest.

At the University of Miami Miller

School of Medicine, we have developed one of the largest PAE practices in North America. From the outset, we applied a multi-disciplinary approach, working with the department of Urology to better evaluate and identify optimal candidates for PAE. This effort allowed our urology colleagues to evaluate the data regarding PAE’s safety and efficacy and observe, first-hand, the benefit provided to patients who otherwise were not surgical candidates. We have continued to take this multidisciplinary approach by creating data-driven PAE educational materials to build relationships with local urologists and primary care physicians in academia and the community.

At our institution, we have performed more than 850 PAE procedures since 2014, and we currently see over 250 PAEs per year. We have consistently optimised

success rate in the Imipenum Cilastatin group (p=1).

Both embolic materials resulted in a significant decrease in pain WOMAC and total WOMAC scores at six months compared to baseline (p<0.05), and the effect of GAE on pain WOMAC and total WOMAC scores was sustained until the 24-month follow-up visit in both groups (p<0.05).

Relating the adverse events, Bhatia commented: “Minor events included transient cutaneous colour change [in five patients] or transient leg numbness observed in one patient], and was only identified after GAE with Embosphere microsphere particles (p=0.00387), which resolved spontaneously at onemonth follow-up (Clavien-Dindo classification grade I).” There were no major adverse events.

Genicular artery embolization has potential to provide midterm relief of pain for patients with mildto-moderate knee osteoarthritis resistant to conservative management.”

our technique and standardised our preprocedural evaluation and post-procedure follow-up to create a robust clinical practice. Additionally, we have moved to a primarily radial (left wrist) approach.

This access is optimal for most patients as it allows immediate ambulation, faster recovery, and features lower risks overall compared to the femoral approach. In addition, we have performed over 250 procedures in a surgery centre with no incidence of need for transfer to the hospital.

Our team is excited to be at the forefront of research in PAE and contribute to the broader interventional radiology and urology communities.

The University of Miami Miller School of Medicine hosted Evolution: Miami 2019 [15–17 November, Miami, USA], a multi-disciplinary conference with over 270 attendees, at which PAE best practices and current debates were discussed by international leaders. Over the past decade, we have presented more than 50 manuscripts on PAE at national and international conferences and in peer-reviewed journals. Recognising the necessity of high-quality data to advance the field, we are delighted to be sharing our results in the presentation titled “Prostate Artery Embolization—Single centre experience of 576 patients with five years follow up” at SIR 2021 [20–26 March, online]. To our knowledge, this is the largest series of the patients treated with PAE in North America presented to date.

Brian Malling (Rigshospitalet, Copenhagen, Denmark) et al conducted a meta-analysis and evaluated the clinical outcomes of 1,254 patients who underwent PAE and found that PAE improved International Prostate Symptom Score (IPSS) by 67% at 12 months

and reduced prostate volume by 32% at three months. Several high-quality randomised control trials evaluating PAE versus transurethral resection of the prostate (TURP) have shown consistent and reproducible results. Most recently, Gabriel Knight (Northwestern University, Chicago, USA) et al performed a metaanalysis comparing PAE and TURP and found no significant differences between changes in IPSS, IPSS quality of life, and erectile function.

Future developments in PAE include: gaining a greater understanding of the effects of PAE on ejaculatory dysfunction, performing a randomised control trial comparing PAE with Holmium laser enucleation of the prostate (HoLEP; the current gold-standard size-independent prostate procedure), and evaluating the long-term durability of the procedure. We hope that the development of research will provide the American Urology Association (AUA) the required evidence to recommend PAE as a treatment option.

Research on PAE has developed from a small case series to a multicentre international effort over the past decade.

We are excited to have built a robust multidisciplinary clinical practice, to have contributed to the literature, and to be a part of further developments to bring this minimally invasive treatment option to more patients with BPH. Shivank Bhatia is professor of Interventional Radiology and Urology at the University of Miami Miller School of Medicine, Miami, USA. Vedant Acharya is a fourth year medical student and past Interventional Radiology Research Fellow at the University of Miami Miller School of Medicine, Miami, USA.

March 2021 | Issue 81

22 Radioembolization

Personalised treatment planning “the future” of radioembolization, ECIO hears, in Y-90 vs. Ho-166 comparison Individualised treatment selection and planning based on controlled dosimetry will lead to improvements in treatment accuracy. This is the conclusion presented

by Marnix Lam (University Medical Center Utrecht, Utrecht, The Netherlands) at ECIO Virtual (27 January, online), a series of afternoon webinars that the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) are hosting in lieu of the 2020 European Conference on Interventional Oncology (ECIO). Lam spoke on the differences between Yttrium-90 (Y-90) and Holmium-166 (Ho-166) radioembolization, and told delegates that it was “very important” to ensure interventionalists conduct a “good” scout procedure with control over selection and planning.

CURRENTLY, THERE ARE THREE microspheres available for radioembolization treatment in Europe: TheraSphere (Boston Scientific), SIRSpheres (Sirtex), and Quiremspheres (Terumo). Lam began his talk by highlighting several differences between these microspheres. “Firstly,” he said, “the isotope. This is Y-90 for TheraSphere and SIR-Spheres, and Ho-166 for Quiremspheres.”

Importantly, he said, the different isotopes have different characteristics. Relative embolic effect is lowest for TheraSphere, middling for Quiremspheres, and highest for SIR-Spheres. This is because the number of particles that are injected differs for each microsphere brand: five million for TheraSphere, 50 million for SIRSpheres, and 20 million for Quiremspheres.

Lam explained: “Typically for Theraspheres, there is a low embolic effect, because we only administer around five million particles. With SIR-Spheres, there is a higher embolic effect, because we administer up to 50 million particles, ten times the number of particles as with TheraSphere. With Quiremspheres, we are somewhere in between, with a medium embolic effect, as we administer around 20 million particles.

This means that the specific activity of TheraSphere is much higher: so, the activity per sphere is much higher for Therasphere than it is for SIR-Spheres, and Quiremspheres is again somewhere in between.”

He cited the specific activity for each microsphere as: 1,250–2,500Bq/microsphere for TheraSphere, 50Bq/microsphere for SIR-Spheres, and 200–400Bq/ microspheres for Quiremspheres.

“What does this mean?” Lam asked rhetorically.

“This is really important to understand”. Preclinical work by Alexander Pasciak (Johns Hopkins University, Baltimore, USA) et al in pig livers investigated the use of different numbers of microspheres over the same overall radiation activity (i.e., the same Gy in total; so, when few microspheres were used, they each have a high specific activity, and when large numbers of microspheres were used, they each had a low specific activity). When relatively few microspheres were injected, there was a very heterogeneous distribution pattern. In contrast, when a large number of

microspheres were injected into the liver, each with a low specific activity, the distribution pattern was much more homogenous across the organ.

Liver tolerance of the same radiation activity (as measured in Gy), the same absorbed dose, is therefore greater when fewer particles are injected, each with a higher specific activity. The more homogenous distribution of radiation in the high-number-ofmicrospheres-injected model means that there is a much more limited area of unaffected liver. As Lam explained at ECIO Virtual, in the low-number-of-microspheres group, certain areas of the liver are “super dead”—have a very concentrated radiation dose—and a large swathe of the liver is unscathed.

“This is exactly the difference between TheraSphere [low particle count] and SIR-Spheres [high particle count],” he said. QuiremSpheres are in between.

Expanding on what this means in terms of tolerability, Lam informed listeners that for glass microspheres, a 100Gy radiation dose to the liver results in a 50% chance of toxicity. The same toxicity risk is attained at a 50Gy radiation dose when using resin microspheres, “so half the absorbed dose to the liver, same chance of toxicity, because the distribution is more homogeneous”. The dose thresholds used for treatment planning therefore vary depending on the type of microsphere used.

Lam commented that this “is a very important message”, and advised the audience “to be very careful when comparing doses between products”.

can be used for the scout dose as for the treatment dose, unlike with Theraspheres and SIR-Spheres. Lam went on to explain the clinical significance of this characteristic of Ho-166.

Typically, ahead of a radioembolization procedure, he explained, the interventionalist will conduct a work-up or scout procedure using Tc-99m MAA (macroaggregated albumin).

The 2017 SARAH trial, an open-label, randomised controlled phase 3 trial investigating the efficacy and safety of selective internal radiotherapy (SIRT) with Y-90 resin microspheres compared with sorafenib in hepatocellular carcinoma (HCC) patients, found no significant difference in survival between the two treatments. In a more recent post-hoc analysis of the SARAH trial, published in Radiology in 2000, AnnLaure Hermann (Université Paris-Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France) et al showed that when the tumour-absorbed dose is at least 100Gy, there is a clear difference in survival between resin microspheres and SIRT. “I think there is quite a spectacular result when you compare groups over 100Gy tumour-absorbed dose or below 100Gy tumour-absorbed dose,” Lam opined.

“However,” he continued, the same study also demonstrated that the correlation between the Tc-MAA distribution and the post-treatment Y-90 distribution was “good in 53% of patients only”. In 20% of patients, there was a medium correlation, and in “as much as 27%

I think there is quite a spectacular result when you compare groups over 100Gy tumourabsorbed dose or below 100Gy tumourabsorbed dose.”

Marnix Lam presents at ECIO Virtual 2021

Interventionalists utilise different imaging modalities for different microspheres

Turning to imaging, Lam explained how, due to differing microsphere characteristics, the imaging modality used for each also varies. Expanding on the clinical implications of this, Lam explained: “The idea of using Ho-166 instead of Y-90 is that Ho-166 has a therapeutic effect very similar to Y-90, but on top of that the element Holmium, like Gadolinium, is chemically a lanthanide, so it is paramagnetic and may be visualised and quantified using MRI [magnetic resonance imaging]. Holmium also emits gamma radiation, that may be used for quantitative SPECT [single photon emission computed tomography] imaging.”

While Y-90 can be imaged using SPECT or positron emission tomography (PET), Lam told ECIO Virtual attendees that the former modality is limited by resolution, and the latter by sensitivity. However, Ho166 can be imaged at low quantities by MRI or SPECT, meaning that with Quiremspheres, the same particles

of patients”, a correlation between Tc-MAA and Y-90 distribution was poor.

“This means if we use Tc-MAA for treatment planning, in only 53% of patients the predicted value of Tc-MAA versus post-treatment Y-90 is sufficient for treatment planning. So, this is quite poor,” Lam noted. “What we learn from this study is that, of course, number one, we have to select patients who will benefit: patients where we can reach a 100Gy absorbed dose.

“But what we also learn from this study is that we gain control by having an improved scout procedure, where the work-up is predictive of the final outcome. I believe this is where Holmium steps in, because instead of Tc-MAA, we use the exact same particles for work-up as we use for the treatment procedure. What we gain is control—over the lung-shunt calculation, and also over the intrahepatic distribution.”

Looking to the future, Lam enthused about personalised treatment planning. “Today, we use single compartment modelling at best,” he said, “aiming for an average absorbed dose within a certain perfused volume, but we really want to go towards multicompartment modelling, differentiating between a tumour-absorbed dose and a normal-liver-absorbed dose in each individual patient. We can use the scout dose procedure, the imaging that we gain, by selecting our patients based on a safe normal-liver-absorbed dose and a sufficient tumour-absorbed dose. If we are not able to reach that, we should seek an alternative treatment; so, selection comes first, and, secondly, we should plan our treatment accordingly. This is very important.”

March 2021 | Issue 81

24 Interview

Profile

Parag Patel

From an early understanding in medical school that interventional radiology (IR) was “the future”, Parag Patel has dedicated his career to the discipline, notably as a primary investigator of the BEST-CLI and ATTRACT trials, and now as the incoming president-elect of the Society of Interventional Radiology (SIR). He has also been integral to the design and implementation of a universal IR education curriculum in the USA. In so doing, he has played a large part in shaping that future he once envisioned.

What initially drew you to interventional radiology?

I entered medical school with no knowledge of the field.

I loved patient care but wanted to be able to treat the pathology as well. All of my medical school research was done within vascular surgery. During my surgery clerkship, we routinely followed our patients for tests or studies. One such patient had a postoperative bleed and I assumed we would go back to the operating room, but instead we ventured down to “Special Procedures” (a thankfully historic term for interventional radiology [IR]). Marc Borge successfully embolized the bleeding source. That was my first exposure to angiography and the opportunities that it provided—I was hooked. That was such a light bulb moment for me. IR was the future.

Innovative, elegant, minimally invasive, and, in my mind, the future of medicine. I was all in.

Who have been important mentors throughout your career?

My parents instilled in me a genuine work ethic as well as respect and appreciation of your fellow persons. They gave up so much certainty to provide for me and my brother as immigrants to the USA. Much of who I am today is because of them.

With regards to IR, Marc Borge introduced me to the specialty and fostered a young, naïve, but genuinely interested trainee. Nicos Labropoulos served as a research mentor and emphasised the importance of good science and knowing the data. As a resident, Marc invited me to attend the local Chicago angioclub, which at the time had many leaders in the field that impressed on me the ingenuity and novelty of the specialty. I was fortunate to train at Miami Vascular. Jim Benenati and Barry Katzen led a phenomenal group of faculty that instilled the importance of true clinical practice, exhibiting leadership and grace under pressure. I was privileged to join the group in Milwaukee and continue my growth under the leadership of Bill Rilling, Sean Tutton, Rob Hieb, Eric Hohenwalter, and soon after Sarah White, formed a small but formidable group of interventional radiologists that grew our clinical practice. We supported each other’s research, education, and clinical efforts through a model of shared leadership.

I was very fortunate to receive support from gracious mentors, and can only hope to serve a similar guiding role for other young trainees. This is much of the driving force behind my desire to continue as programme director of our vascular and interventional radiology (VIR) fellowship [that of the Society of Interventional Radiology (SIR)], and now IR residency training programmes.

You have been a primary investigator of the BEST-CLI trial since 2014. Why is this study important?

The BEST-CLI trial (Randomised, multicentre, controlled trial to compare best endovascular versus best surgical therapy in patients with critical limb ischaemia) completed enrolment over a year ago and strives to complete follow-up during the coming year. The study is important as we have very limited

high-quality data on the management of critical limb ischaemia (CLI) patients, specifically comparing best surgical versus best endovascular treatments. Our multidisciplinary collaborative practice at the Medical College of Wisconsin (MCW) has routinely followed a shared model of decision making with surgical and endovascular strategies employed in our local practice.

Our involvement in BEST-CLI was seen as a natural extension of our practice and may shed light on how to best treat these patients or support how we already practice. Further studies in this space are needed to allow for a more structured and uniform algorithmic approach to be taken in the care of these patients.

As an ATTRACT trial investigator, what did this experience teach you, and how has clinical practice been impacted by these findings?

I learned much from my involvement in ATTRACT (Acute venous thrombosis: thrombus removal with adjunctive catheter-directed thrombolysis), namely, the exhaustive work it takes to consistently beat the drum

We continue to have much work to do in placing the treatments we provide within the algorithm of management for the diseases we treat.

Early on, we struggled with maintaining a hold on our procedures, when maintaining a hold on our patients should have been the focus.” for screening, enrolment, and follow-up and see a trial through to completion. Much credit goes to Suresh Vedantham for his leadership and effort. We struggled with maintaining clinical equipoise in the trial. We were studying the role of an approved treatment in the hopes of identifying a benefit for our patients long term. Many felt they already knew the best course for their patients and enrolment would prevent proper treatment if they randomised to the non-intervention arm. Nonetheless, the trial did not support routine use of pharmacomechanical catheter-directed thrombolysis (PCDT) for all acute lower extremity deep venous thrombosis (DVT) for prevention of post-thrombotic syndrome (PTS). This has helped inform our practice algorithm, as we no longer offer PCDT for isolated femoropopliteal DVT or in older patients with acute iliofemoral DVT (aside from those with phlegmasia).

We will treat younger patients with symptomatic acute iliofemoral or iliocaval DVT in the hopes of improving

acute symptoms and minimising the severity of PTS.

As chair of the SIR Residency Essentials Advisory Committee, you have been central to the development of the new online curriculum. What was this experience like?

The Residency Essentials project came about through a strategic planning exercise for the SIR. As Graduate Medical Education Councillor during the time of our IR Residency implementation, I was tasked to champion support for the new training model. The idea of a universal IR education curriculum available for all IR trainees aimed to minimise the significant differences in training experiences across the country. While the technical experiences may vary from institution to institution, the fundamental knowledge base of disease management, role of interventional therapies, and management of these patients could be taught

Issue 81 | March 2021

Interview 25 to all trainees nationally. The project was a massive undertaking with cross-divisional collaboration within the SIR and significant staff support. It took over three years and a number of physician volunteers to develop the extensive curriculum outline, identify and curate content (video lectures, timely reviews, and assessment questions), and then neatly package them into modules available on a new learning management system. The project launched in July 2020 to great success. The content will continually be reviewed and periodically updated. The timing of this launch was in the midst of the pandemic and coincided with distance learning mandates across the country. The new Residency Essentials fits this quite nicely as it is an online curriculum. Now that the curriculum is complete, we have the opportunity to support IR education efforts abroad.

You are stepping into the role of president-elect of the SIR. What are your ambitions for the society in the coming years?

SIR, like any big organisation, is a big ship and abrupt changes are not easily handled. I hope to make incremental improvements to the organisation to better serve our members. Namely, we will continue to grow our education and research efforts, and increase awareness of IR treatments to patients and the value of IR to health systems.

What is the greatest challenge currently facing interventional radiologists?

We continue to have much work to do in placing the treatments we provide within the algorithm of management for the diseases we treat. Early on, we struggled with maintaining a hold on our procedures, when maintaining a hold on our patients should have been the focus. If we all agree that minimally invasive, image-guided interventions are the future, then we cannot complain if others adopt this strategy as long as they do it well. I think a bigger concern is why some of our proven therapies still remain outside the standard management guidelines of basic disease entities. This requires a long view with a strategic approach and collaboration amongst our stakeholders to accomplish. I believe we can do it.

alisonlang.com

What are your hobbies and interests outside of medicine?

Training:

n 1998–2002: MD, Loyola Stritch School of Medicine, Maywood, USA n 2003–2007: Diagnostic Radiology resident, Loyola University Medical Center, Maywood, USA n 2007–2008: Vascular and Interventional Radiology (VIR) Fellow, Miami Cardiac & Vascular Institute, Miami, USA

Faculty Appointments:

n 2020–present: professor of Radiology & Surgery, Medical College of Wisconsin (MCW), Milwaukee, USA n 2017–present: programme director of IR residencies, MCW, Milwaukee, USA n 2012–present: Medical Student IR Interest Group, Faculty Mentor, MCW, Milwaukee, USA

Art, architecture, and industrial design. I am also an avid traveller, immersing myself in new cultures and enjoy any time spent in nature. Prepandemic, I have hiked the narrows at Zion National Park, down to the Colorado River at the Grand Canyon, trekked the Inca Trail to Machu Picchu, and am now (hopefully) planning a summit of Mount Kilimanjaro for next year. Family time is a priority, and I enjoy cooking up new recipes with my wife, Mona, or rallying tennis balls on the court with my two daughters, Simrin (age 12) and Siana (age nine).

Society of Interventional Radiology (SIR) leadership:

n 2021–2022: President-elect, SIR Executive Council n 2017–present: Co-chair, Residency Essentials Advisory Committee n 2016–2020: Course director, SIR Lower Extremity Arterial Revascularisation (LEARN) n 2015–2020: Councilor, Graduate Medical Education

March 2021 | Issue 81

26 Artificial intelligence in IO

Artificial intelligence should be incorporated into interventional oncology curricula to advance the specialty, BSIR hears

Artificial intelligence aids registration during ablative procedures

“Artificial intelligence [AI] is changing the face of healthcare for all stakeholders, from consumers to providers,” Stephen Hunt (University of Pennsylvania, Philadelphia, USA; co-founder of the Penn Image-guided Interventions Laboratory) told attendees of the virtual 2020 annual scientific meeting of the British Society of Interventional Radiology (BSIR; 1–3 December 2020, online).

Speaking during a “State of the Art” session on the future of interventional oncology (IO), Hunt detailed how “the era of AI” will expand the horizons of interventional oncology.

A

ccording to Hunt, the growth of US Food and Drug Administration-approved AI tools in the coming decade “will be exponential”. He urges interventional radiologists to stay abreast of the developments by integrating AI concepts into medical education: “Users must be educated not only on the proper application of these AI tools and on their limitations,” he said, “but on the mechanisms for validating their efficacy.

Foundational concepts in statistics and bioinformatics are critical to responsible adoption and use of AI. Collaboration with developers of these tools will improve their clinical relevance and usability to interventional radiology. IO educators and faculty should incorporate AI topics into their curricula and research.”

He defines AI simply: “Really, it is just using computers and software to perform tasks that normally require human intelligence to accomplish. That seems like a very broad definition, and it is—it is somewhat vague on purpose, because it encompasses such a large field.”

Machine learning is a concept integral to AI: it describes the process of a computer learning from experience as it goes through data sets. A machine learning algorithm will learn to make connections between data points or perform some sort of classifier task, such as image recognition, when fed data, and gets better at its designated job the more input it is fed.

“The real breakthroughs for interventional oncology will require assembling and curating larger datasets,” Hunt therefore explained to delegates.

In addition to a large amount of data and a machine learning algorithm (or another tool designed to perform sophisticated calculations, such as a neural network), AI also requires some technical expertise, he continued. The end user has to be able to interpret the output generated by the AI software in order to apply the information to clinical practice.

Hunt provided some examples of AI use in the interventional oncology space.

Intraprocedural spatial localisation

Firstly, he talked the BSIR audience through an example where an interventionalist brings in a patient with a gastrointestinal (GI) bleed. Whilst the imagined patient is lying on the angiography table, the interventional radiologist needs to identify the location of the bleed on a CT scan in order to then stop the blood flow. Hunt suggested that an algorithm could be used in image registration and segmentation: this would enable the fluoroscopy unit to automatically identify the area where it predicts the bleed would appear.

“This kind of technology already exists, it has just not been put to use in clinical practice,” Hunt said. “It has not really been deployed that way.

“In addition, you could take those images [from prior GI bleed angiography studies] and train an AI with them—we have done this in our lab, and other labs have done this too—so automatically you have a classifier that will show you where the bleed is on the image. It is able to learn from some prior database that we made of GI bleed images, and then we can try it on new cases.”

Clarifying this point specifically to Interventional News, Hunt elucidates: “The point is for your angio suite to automatically detect the bleed during angiography and ‘circle it’ or otherwise provide a target sign to point it out to your eye. That way the interventionalist can go to that spot to drop a coil.

“I think within the next five years you are going to see a lot of these tools from the larger vendors, like Siemens and Philips.”

CT perfusion imaging during TACE

Giving another example, Hunt next discussed AI in CT perfusion imaging during transarterial chemoembolization (TACE).

Stephen Hunt presenting in person at BSIR 2019

“We always have this problem of, during a TACE, how do you know you have full treatment of the tumour? One of the ways would be to do CT perfusion on that patient at the time of TACE. We have one of these image hybrid rooms, we have all the technology there, we have CT perfusion on that CT scanner, which is in the hybrid room of the fluoroscopy CT unit, but it has not been integrated into the workflow, the technicians do not know how to use it—it is these kinds of problems that we have not yet worked out. This is an example where you can have that real-time critical feedback, [as the AI] tells you ‘hey, there is an

Users must be educated not only on the proper application of these AI tools, but on the mechanisms for validating their efficacy.”

area of tumour that you have missed’.

The CT perfusion would give you that information.

Intraprocedural augmented reality

Turning to an example he said is more in the research and development phase, Hunt discussed the use of augmented reality intraprocedurally. The HoloLens, from Microsoft, is a set of goggles that the interventionalist could wear that allows them to see virtual projections superimposed over the real world.

There are various methods of registration when it comes to correctly superimposing the projected image on to a patient, which utilises AI. Hunt described how the physician could select a point on the patient’s skin, and a point in the tumour on the projection, and the HoloLens will allow the user to visualise a path that will give them an angle to register their ablation probes. This can be combined with the breathing cycle and cardiac gating, so probe advancement only takes place at the correct time in the cycle. Hunt highlighted work that Imactis and Xact are doing in this space, and encouraged listeners to look into these companies.

March 2021 | Issue 81

28 Transarterial chemoembolization

TACE

TACE with drug-eluting microspheres as “safe and effective” as conventional TACE, pooled analysis shows The sustained release of anthracyclines and durable embolization from LifePearl microspheres (Terumo Europe) makes transarterial chemoembolization (TACE) with these embolic agents a safe and effective treatment option for patients with early and intermediate stage hepatocellular carcinoma (HCC). This was the conclusion presented by Filipe Veloso Gomes (Hepatobiliary-pancreatic and Transplant Center, Hospital Curry Cabral, Centro Hospitalar Universitario de Lisboa Central, Lisbon, Portugal) at the 2021 meeting of the Society of Interventional Oncology (SIO; 3–5 February, online).

TODAY, TACE IS INDICATED FOR THE treatment of unresectable HCC, according to the latest European Society for Medical Oncology (ESMO) clinical practice guidelines, with level IA evidence for Barcelona Clinic Liver Cancer (BCLC) stage B

Filipe Veloso Gomes presenting at SIO

tumours (intermediate stage tumours), and level IB evidence for tumours categorised as BCLC 0–A (early) stage. TACE is recommended for patients awaiting liver transplants.

Veloso Gomes and his colleagues set out to assess contemporary interventional oncology practice in HCC, and conducted a pooled analysis of patient-level data from more than 550 patients with this liver cancer, enrolled across five different single-arm studies and treated with anthracyclines-loaded LifePearl.

Safety was assessed by close monitoring of adverse events, according to the Common Terminology Criteria for Adverse Events (CTCAE). Tumour response was evaluated following hospital practice, according to mRECIST (modified Response Evaluation Criteria In Solid Tumours; used in four studies) and RECIST1.1 (in one study) and analysed as best overall response.

Kaplan-Meier analysis was used to estimate event rates for time-to-event outcomes: progression-free survival, time to un-TACE-able progression, and overall survival.

Of the 586 patients included in the study, 57% were in BCLC 0/A stage, which the presenter said “clearly demonstrates the indication for TACE in a wide

Conventional transarterial chemoembolization more costeffective than drug-eluting embolic TACE Compared with doxorubicin-loaded drug-eluting embolic transarterial chemoembolization (DEE-TACE), conventional transarterial chemoembolization (cTACE) yielded a higher number of quality-adjusted life years (QALY) at a lower cost, making it the more cost-effective of the two modalities. This is the conclusion reached by a cost-effectiveness analysis published in the Journal of Vascular and Interventional Radiology (JVIR) by Xiao Wu (Yale School of Medicine, New Haven, USA), senior author Nishita Kothary (Stanford University Medical Center, Stanford, USA) et al.

T

he investigators set out to compare the cost-effectiveness of DEE-TACE versus cTACE for patients with unresectable hepatocellular carcinoma (HCC).

They constructed a decision-analysis model that spanned a payer’s entire life; the model simulated the clinical course of patients with unresectable HCC, including periprocedural complications, additional transarterial chemoembolization or other treatments (ablation, radioembolization, or systemic treatment), palliative care, and death.

Describing their methodology, Wu et al explain: “All clinical parameters were derived from the literature. Base case calculations, probabilistic sensitivity analyses, and multiple two-way

sensitivity analyses were performed.” cTACE yielded a health benefit of 2.11 QALYs at a cost of US$125,324, whereas DEE-TACE yielded 1.71 QALYs for US$144,816. In 10,000 Monte Carlo simulations, cTACE continued to be more cost-effective.

The authors report that cTACE was cost-effective when the complication risks for both the procedures were simultaneously varied from 0–30%.

DEE-TACE became cost-effective if the cTACE mortality exceeded that of DEE-TACE by 17% in absolute values. The two-way sensitivity analyses demonstrated that cTACE was cost-effective until the risk of disease progression was >0.4% of that for DEETACE in absolute values.

spectrum of patients”.

Adverse events were reported in 197 (33.6%) patients; the majority of these (23.3% of all patients) were grade 3. A further 2.3% were grade 4, and 1.5% were grade 5. The most frequent adverse events were related to postembolization syndrome. Hepatobiliary toxicities were detected in 6.9% of all patients. Veloso Gomes therefore told SIO delegates that there was “a good tolerability and acceptable toxicity” of TACE with LifePearl.

In addition, he commented: “Hepatobiliary toxicities as [assessed by] imaging findings were lower than with other drug-eluting microsphere TACE [procedures] and similar to conventional TACE studies.” He specifically mentioned the recently published, prospective PARIS registry in his talk, which reported a higher hepatobiliary toxicity of 12.9% (in 30 of 233 procedures). Veloso Gomes noted that this 12.9% toxicity rate was still lower than that published in the literature from previous studies of drug-eluting microsphere TACE, and was more comparable to the rate seen in conventional TACE (cTACE) procedures.

He continued: “There was a high tumour response rate [in the pooled analysis that was the key focus of his presentation] that translated into promising progression-free survival, time to un-TACE-able progression, and overall survival. The overall survival observed in this analysis is among the best overall survival observed in recent TACE trials and metaanalyses.”

The presenter also cited some limitations to their methodology, which boil down to the fact that this pooled analysis was not planned prior to conducting the individual studies. Therefore, he said that there was heterogeneity in the populations enrolled, as well as differences in the recording of variables, including frequency, timing, type of imaging, and follow-up duration.

“Our analysis showed that DEETACE would be more cost-effective if it offered >2.5% higher overall survival benefit Nishita Kothary than cTACE in absolute values,” Wu and colleagues summarise.

Speaking to Interventional News, Kothary comments: “Data on bland embolization are limited, precluding a robust carcinoembryonic antigen (CEA) test. DEE-TACE is also associated with a higher need for pain control due to its true embolic nature (I would guess that bland embolization is similar), and pain control often requires overnight hospitalisation that would impact a CEA.” Replying on Twitter, Aaron Maxwell (The Warren Alpert Medical School of Brown University, Providence, USA) asked: “If cost-effectiveness is being

We simply have to aggressively expand our science and transform our therapies.”

discussed, why not bland embolization alone? No chemotherapy to pay for, and RCT [randomised controlled trial] data with equivalent outcomes to TACE from 2016.”

Study co-author Julius Chapiro (also Yale School of Medicine, New Haven, USA) responded: “Excellent point!

While there is some doubt as to the standard of care for the control arm in the JCO [Journal of Clinical Oncology] paper, I am not at all convinced that chemo adds value to beads. Our experimental studies prove the point, too.

We must really think about it in depth.

“I will say that my journey so far has really made me doubt the value of chemo. We now need to understand the immunological effect of the different materials we introduce and how they may or may not affect the tumour microenvironment and immune response. I do not see clear striking evidence for DEBs re outcome. None.”

This prompted Maxwell to reply: “Terrific work. I think it is incumbent upon the IR [interventional radiology] research community to aggressively expand our understanding of the tumour microenvironment if we are to optimise outcomes for catheter-directed locoregional liver therapies.”

Chapiro agreed: “We simply have to aggressively expand our science and transform our therapies to be directed to and tailored for the individual tumour microenvironment!”

March 2021 | Issue 81

30 Liquid biopsy

Liquid biopsy and whole-body MRI: A crossing of paths Bruno Damascelli Vladimira Tichà Gianluigi Patelli Giuseppe Petralia Comment & Analysis A combination of liquid biopsy and whole-body magnetic resonance imaging (WB-MRI) could revolutionise cancer diagnostics and monitoring, write Bruno Damascelli, Vladimira Tichà, Gianluigi Patelli, and Giuseppe Petralia. Here, they detail the potential advantages of these non-invasive techniques: “The combination of magnetic resonance and liquid biopsy may potentially solve some diagnostic conflicts and guide new treatments based on molecular diagnosis and its variations as the cancer evolves”.

M

odern cancer diagnostics aim to provide improved sensitivity, specificity, and disease localisation, without any risk of biological harm. Liquid biopsy and whole-body magnetic resonance imaging (WB-MRI) are both in an accelerated phase of development as promising, non-invasive methods for early cancer diagnosis and monitoring. A combination of the two methods could prove advantageous.

The genetic profile of a tumour extracted from a blood sample seemed to be the endpoint for cancer diagnosis, disease monitoring, and selection of targeted molecular treatments.

However, liquid biopsy results are not easily reproducible at present because tumours release minimal amounts of fragmented DNA into the circulation in an unpredictable manner. Molecular diagnosis based on biological liquids is complementary to tissue biopsy and cannot replace it. Yet liquid biopsy has unique advantages, such as the ability to demonstrate changes in the heterogeneity of the cancer genome and to detect circulating tumour cells (CTC) with intact DNA, which are prognostically significant.

The most widely used imaging methods in oncology are based on ionising rays, making it undesirable to resort to these methods for screening and for frequent disease monitoring, especially in young patients and women of fertile age. Since its introduction, magnetic resonance imaging has developed surprising abilities to distinguish between normal and tumour tissue without unwanted effects.

Diffusion sequences reflect the restricted mobility of water protons that occurs in some tumours because of their greater cell density. The consequent increase in contrast between tumour and normal tissue allows spatial localisation of

who undergo diffusion whole body (DWB)-MRI screening makes this test interesting, although findings calling for further investigation may be produced in as many as 30% of those screened, according to published data.

Similarly, liquid biopsy, as conventionally applied in patients without a cancer diagnosis, is unable to provide direct topographical information, although identification of a tumourrelated mutation in the blood is of considerable diagnostic significance.

For liquid biopsy, tumour DNA extraction can be improved through enrichment methods currently being developed and through detection of other tumour markers, such as newgeneration protein biomarkers, and cancer metabolites identifiable by mass spectrometry.

We endeavour to improve the sensitivity of liquid biopsy through selective venous sampling from the vessels draining the district or various districts affected by the tumour, thus reducing the impact of the dilution of fragmented DNA that occurs in the total blood volume.

nodes, spleen, and bone marrow were unremarkable. Given the difficult access for instrumental biopsy, liquid biopsy with selective venous catheterisation was suggested. Only the sample from the left internal iliac vein was positive for the FGFR3 gene mutation, related to lymphoma. Subsequent percutaneous computed tomography (CT)-guided biopsy and a video-laparoscopic procedure were both non-diagnostic.

Blood tests were normal, while an 18F-FDG positron emission tomograohy (PET) scan showed positive uptake coinciding with the MRI finding. No progression was seen at follow-up.

Case 2

A 50-year-old male presented with persistent thrombocytopenia. Liquid biopsy performed as a preliminary test showed BRAF gene mutation in selective venous samples and in peripheral blood.

This mutation is related to lymphoma in 2.23% of cases. Low-grade lymphoma was confirmed by bone marrow biopsy.

Chemotherapy led to the disappearance of the mutation in liquid biopsy samples, whereas a repeat bone marrow biopsy

Case 1 Figure 1.

Left: Left external iliac lymph node measuring 27x27mm, hyperintense in high-b-value (900s/mm2) diffusion-weighted images.

Centre: The same lymph node and other suspicious lymph nodes measuring <10mm can be seen in the left common iliac chain in maximum intensity projections of the diffusionweighted images.

Right: Selective blood sampling from the left internal iliac vein.

Liquid biopsy and wholebody magnetic resonance imaging are both in an accelerated phase of development as promising, noninvasive methods for early cancer diagnosis and monitoring.” the cancer. The increased sensitivity and specificity of diffusion-weighted WB-MRI has been demonstrated in cancer patients, but the data on healthy subjects are still preliminary. The possibility of diagnosing cancer in the 1–2% of asymptomatic subjects

Case 2 Figure 2.

Maximum intensity projections of the diffusion-weighted images show diffuse but mild bone marrow changes mainly in the spine, pelvis, and femurs, compatible with the underlying lymphoproliferative disease.

Case 1

A 46-year-old male with no personal or family history of cancer underwent diffusion-weighted WB-MRI in the context of clinical screening, which revealed enlarged lymph nodes in the left iliac chain. The remaining lymph

confirmed minimal disease. Diffusionweighted WB-MRI revealed diffuse discrete lesions in the bone marrow, mainly in the spine and pelvis.

Case 3

Liquid biopsy was performed in a

Issue 81 | March 2021

Cooled radiofrequency ablation 31

Case 3 Figure 3.

Axial high-b-value (900s/mm2) diffusion-weighted images (left) and maximum intensity projections (centre) show an enlarged (21x11mm) right supraclavicular lymph node.

Right: The sampling position in the inferior vena cava.

necessarily mean that cancer will develop in that person’s lifetime. On the other hand, the diagnostic and prognostic significance changes when a diagnosis of minimal residual disease or recurrence of disease cannot otherwise be obtained at sites inaccessible to conventional instrumental biopsies. The combination of magnetic resonance and liquid biopsy may potentially solve some diagnostic conflicts and guide new treatments based on molecular diagnosis and its variations as the cancer evolves.

Bruno Damascelli and Vladimira Tichà are interventional radiologists in the department of Interventional Oncology, Emo GVM Centrocuore Columbus, Milan, Italy.

77-year-old asymptomatic female with a close family history of ovarian cancer.

The peripheral sample was negative, whereas blood obtained from the inferior vena cava showed the PTEN gene mutation. This mutation is related to ovarian cancer in 3.5% of cases. On DWB-MRI, a right supraclavicular lymph node was enlarged with respect to a previous chest CT scan performed for other reasons. Lymph node biopsy was negative for epithelial cells or lymphoproliferative disease.

Gynaecologic examination, transvaginal ultrasound, and abdominal CT scan were all negative. In this case, the liquid biopsy result may be the expression of a tumour clone not destined to develop into

progressive ovarian cancer. The finding of the mutation in the sample collected from the blood draining the pelvis nonetheless reinforces the ovarian origin of pathological DNA. Follow-up over time is recommended.

Diffusion-weighted WB-MRI has already earned its place in cancer diagnostics for staging of multiple myeloma and malignant lymphomas, thanks to its ability to depict the bone marrow and skeletal lesions due to solid tumour metastases. In any case, the high contrast resolution of MRI makes it an important alternative for other difficult evaluations, such as peritoneal cancer seeding, for example. The potential value of this imaging method in asymptomatic

We endeavour to improve the sensitivity of liquid biopsy through selective venous sampling.” patients remains to be established.

Likewise, liquid biopsy can hardly be accepted as the sole initial diagnostic method in asymptomatic patients and those with no previous history of cancer because tumour-related mutations, which are defined as transient, do not

Novel technique “stuns” arthritis pain in shoulder and hip A novel outpatient procedure—cooled radiofrequency ablation (c-RFA)—offers lasting pain relief for patients suffering from moderate to severe arthritis in their hip and shoulder joints, according to a study presented at the annual meeting of the Radiological Society of North America (RSNA; 29 November–5 December 2020, online). Researchers said the procedure could help reduce reliance on addictive opiates.

PEOPLE WITH MODERATE TO SEVERE PAIN related to osteoarthritis face limited treatment options.

Common approaches like injections of anaesthetic and corticosteroids into the affected joints grow less effective as the arthritis progresses and worsens.

“Usually, over time patients become less responsive to these injections,” say study authors Felix M Gonzalez and Omar N Kallas (both Emory University School of Medicine, Atlanta, USA). “The first anaestheticcorticosteroid injection may provide six months of pain relief, the second may last three months, and the third may last only a month. Gradually, the degree of pain relief becomes non-significant.”

Without pain relief, patients face the possibility of joint replacement surgery. Many patients are ineligible for surgery because of health reasons, whereas many others choose not to go through such a major operation.

For those patients, the only other viable option may be opiate painkillers, which carry the risk of addiction.

Gonzalez and colleagues have been studying the application of a novel interventional radiology treatment, c-RFA, to achieve pain relief in the setting of advanced degenerative arthritis. The procedure involves the placement of needles where the main sensory nerves exist around the shoulder and hip joints. The nerves are then treated with a low-grade current known as

radiofrequency that “stuns” them, slowing the transmission of pain to the brain.

For the new study, 23 people with osteoarthritis underwent treatment, including 12 with shoulder pain and 11 with hip pain that had become unresponsive to anti-inflammatory pain control Felix M Gonzalez and intra-articular lidocainesteroid injections. Treatment was performed two to three

We are just scratching the surface here. We would like to explore efficacy of the treatment on patients in other settings, like trauma, amputations, cancer.”

Gianluigi Patelli is the chief of the Radiology Department at Seriate Hospital, Seriate (BG), Italy.

Giuseppe Petralia is director of the Precision Imaging and Research Unit, IEO European Institute of Oncology, IRCSS, Milan, Italy, and is an interventional radiologist in the department of Oncology and Haematology, University of Milan, Milan, Italy, and at Advanced Screening Centers, ASC Italia, Castelli Calepio, Bergamo, Italy.

This work is sponsored by the Falciani Foundation. The authors report no disclosures pertaining to this article.

weeks after the patients received diagnostic anaesthetic nerve blocks. The patients then completed surveys to measure their function, range of motion, and degree of pain before and at three months after the ablation procedures.

There were no procedure-related complications, and both the hip and shoulder pain groups reported a statistically significant decrease in the degree of pain, with a corresponding increase in dynamic function after the treatment.

“In our study, the results were very impressive and promising,” Gonzalez enthuses.

“The patients with shoulder pain had a decrease in pain of 85%, and an increase in function of approximately 74%. In patients with hip pain, there was a 70% reduction in pain, and a gain in function of approximately 66%.”

The procedure offers a new Omar N Kallas alternative for patients who are facing the prospect of surgery. In addition, it can decrease the risk of opiate addiction.

“This procedure is a last resort for patients who are unable to be physically active and may develop a narcotic addiction,” Gonzalez comments. “Until recently, there was no other alternative for the treatment of patients at the end of the arthritis pathway who do not qualify for surgery or are unwilling to undergo a surgical procedure.”

At last year’s RSNA annual meeting, Gonzalez presented similarly encouraging results from a study of a related procedure for the treatment of knee arthritis.

Together, the knee, shoulder, and hip articulations account for approximately 95% of all arthritis cases.

The procedure could have numerous applications outside of treating arthritic pain, Gonzalez explains.

Potential uses include treating pain from cancer and sickle cell anaemia-related pain syndrome, for example.

March 2021 | Issue 81

32 Imaging

First-in-human study demonstrates “feasibility and potential” of FORS technology

Based on the findings of their first-in-human feasibility study, Joost van Herwaarden (Utrecht University Medical Centre, Utrecht, The Netherlands) and colleagues write in the European Journal of Vascular and Endovascular Surgery (EJVES) that Philips’ Fiber Optic RealShape (FORS) technology “has the potential to improve intraoperative imaging”. Their results show that real-time navigation using FORS technology is safe and feasible in abdominal and peripheral endovascular procedures.

E

ndovascular procedures are conventionally conducted using 2D fluoroscopy. However, a new technology platform, FORS, has recently been introduced, which allows “real-time, 3D visualisation of endovascular devices using fibreoptic technology,” Van Herwaarden et al explain. This technology functions as an “add on” to conventional fluoroscopy and “may facilitate endovascular procedures”. The investigators present the first-in-human study to assess the feasibility of FORS in clinical practice; they performed a prospective cohort feasibility study between July and December 2018, recruiting patients undergoing either regular or complex endovascular aneurysm repair (EVAR) or endovascular peripheral lesion repair.

Van Herwaarden et al used FORS guidance

exclusively during navigational tasks, such as target vessel catheterisation or crossing of stenotic lesions. In EJVES, they write that three types of FORS-enabled devices were available: a flexible guidewire, a Cobra-2 catheter, and a Berenstein catheter. They note that devices were chosen at the physician’s discretion and could comprise any combination of FORS and nonFORS devices.

The primary study endpoint was technical success of the navigational tasks using FORS-enabled devices, and secondary endpoints were user experience and fluoroscopy time.

The authors note that they enrolled 22 patients in the study, comprising 14 EVAR and eight endovascular peripheral lesion repair patients. They detail that, owing to a technical issue during start up, the FORS system could not be used in one EVAR. However, they report that the remaining 21 procedures went ahead without device- or technology-related complications and involved 66 navigational tasks.

Van Herwaarden and colleagues add that in 60 tasks (90.9%), technical success was achieved using at least one FORS-enabled device. In terms of user experience, operators graded FORSbased image guidance “better than standard guidance” in 16 of 21 and “equal to standard guidance” in five of 21 procedures. Finally, regarding fluoroscopy time, the authors report that this ranged from 0 to 52.2 minutes, adding that several tasks were completed without or with only minimal X-ray use.

The authors acknowledge some limitations of the present study. For example, they communicate that, although the operators had experience with the system in preclinical studies, they went through a learning curve during clinical use. Van Herwaarden et

Novel mixed reality dose visualisation system may help manage radiation exposure during IR procedures Mixed reality dose visualisation is expected to improve exposure dose management for interventional radiology (IR) patients and health professionals by depicting invisible radiation exposure in real space, a study published in Journal of Medical Systems reports.

First author Takeshi Takata (Graduate School of Medical Care and Technology, Teikyo University, Tokyo, Japan), senior author Jun’ichi Kotoku (Graduate School of Medical Care and Technology, Central Radiology Division, Teikyo University, Tokyo, Japan) et al examined for the first time in the relevant literature the concept and feasibility of an immersive, real-time dose visualisation system using mixed reality for dose management.

CONTEXTUALISING THIS research, the authors write: “For interventional radiology [IR], dose management has persisted as a crucially important issue to reduce radiation exposure to patients and medical staff.” Currently, IR patient dose management generally uses only a displayed dose area product, they continue, saying that this parameter does not identify the exposed position.

“For that reason, a dose distribution on the patient’s skin cannot be managed,” they note. Similarly, despite measuring the radiation exposure of the health professionals involved in IR procedures with personal dosimeters, Takata and colleagues explain that the dose is unknown until the dosimeter is read out.

“To optimise exposure for all involved, health professionals must note their exposure dose in real time according to each situation,” they claim. “An intuitive, real-time dose management system is expected to facilitate management of the dose and to improve patients’ and health professionals’ medical safety.”

Their mixed reality dose visualisation system uses a wearable mixed reality holographic device (HoloLens; Microsoft). This uses a simultaneous localisation and mapping algorithm for spatial mapping and detection of the wearer’s position, and provides an accurate three-dimensional holographic representation of digital objects with a full sense of depth. The objects

al write: “The optimal visualisation settings (regarding viewing angle, magnification, mono- or biplane mode, and optimal overlay) had to be identified for the different types of procedure.”

In addition, they note that workflow improvements, like the optimal positioning of the system, to work from both the groin and the arm, had to be learned during the study. “In this first study, the technical success would probably have been higher if more than two differently shaped catheters had been available,” they posit.

Van Herwaarden et al list a few more limitations for clinical use: the limited working length of the catheters and guidewire available for this study, and the inability to backload the guidewires. “These issues will be addressed in future releases of the system,” they state.

Finally, they relay that there were technical issues with the FORS equipment during this study. The technology could not be used in one patient,, and using two FORS devices at the same time was impossible in on other patient. They note that these factors “probably affected study results”.

The authors conclude that this exploratory study “demonstrates the feasibility and potential of this technology in clinical practice and forms a foundation for future clinical research.” However, they recognise that comparative studies are needed to “prove and quantify” the benefits and potential radiation reduction for all types of endovascular procedures.

can be seen by a group of viewers simultaneously from all angles.

“Projection of the patient’s skin dose onto the patient’s body and estimation of the health professional’s dose requires accurate tracking of their positions and movements in a room,” Takata and colleagues explain. “Nonetheless, position tracking using an external tracking system is adversely affected by disturbances, such as the movement of staff members and fluoroscopy systems, during a procedure. Therefore, an object recognition tracking method is preferred for [our] mixed reality dose visualisation system.” Using a three-dimensional graphics platform and the object detection and tracking functionalities built into a software development kit, they were able to register images in real time by tracking the relative position and orientation of the real objects using an RGB (red-green-blue) camera on HoloLens; this positional information was then used to update the transformations within the virtual world

An interventionalist wearing the HoloLens goggles

Joost van Herwaarden

for dose projection and estimation.

The number recognition system accurately recognised all displayed fluoroscopic conditions every 0.2 seconds. Validation of the measured values of the sensor unit (judged based on a comparison with the laser sensor value) revealed that averages of the error were less than 0.18% in three directions between the mixed reality dose visualisation system sensors and the laser displacement sensor. Average patient skin dose distribution was estimated within three seconds. The dose distribution was visualised with four seconds latency.

Takata et al describe how the dose distribution appears in practice: “It is depicted as coloured cubes on the skin.

A colour bar shown in the air represents the absorbed dose level. The health professional’s eye lens dose rate was updated continuously. It was indicated as numerical values in the air.”

This led them to conclude: “More than other real-time dose estimation systems for IR, this mixed reality dose visualisation system provides an immersive experience and a detailed depiction of the dose distribution.

Although several visualisation systems can be used for dose distributions, our mixed reality [one] can visualise the dose distribution in three dimensions in front of the user’s eyes. This visualisation mode will help procedures proceed smoothly, because the surgeon need not look at a distant monitor to know the dose.”

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March 2021 | Issue 81

34 COVID-19 and IR

Interventional radiology on the frontlines in 2021: Rising to the challenges ahead Narayan Karunanithy Comment & Analysis Following the rapid reconfiguration of healthcare practices in response to the COVID-19 pandemic in early 2020, Narayan Karunanithy reflects on the position of interventional radiology (IR) services going into 2021. Citing data demonstrating that the reduction in IR activity during the first national lockdown was far less than that seen in other procedure-centred specialties, such as vascular surgery, urology, and endoscopy, Karunanithy argues that formal incorporation of IR treatments into patient pathways would result in more efficient care. As many IR procedures can be performed as a day case or in an ambulatory care unit, he writes that interventional radiologists can “hugely support emergency preparedness plans”, which will likely continue to be vital in 2021.

T

he challenge for healthcare organisations to deliver on the “triple aims” of health system performance has been made many magnitudes more complex in 2020 due to the COVID-19 pandemic (see below table).1 The scope and nature of IR practice, however, is unusually well placed to meet these aims, and looks well set to play a more central role in delivery of high quality, safe healthcare in 2021 and beyond.

At the time of writing, we find ourselves in the midst of the second COVID-19 pandemic wave in the UK, and sadly we are once again already seeing both high infection and mortality rates. The recent promising vaccine results have provided a much-needed glimmer of hope. Whilst vaccines are considered at present our best hope, uncertainty still remains regarding the effectiveness, availability, and impact of those vaccines. Hence, the healthcare strategy—at least for the foreseeable future—will need to incorporate the ability to treat those with COVID-19 and continue to provide timely, safe, effective, and cost-efficient care for everyone with non-COVID related illnesses.

During the first wave, it was impressive and inspiring to see so many IR departments demonstrate a willingness to reconfigure working practice and be available to provide much-needed acute services. One of the models that worked extremely well during the summer/autumn of 2020 was the spatial segregation of services into “low-risk” and “high-risk” sites.

This was, in large part, created through partnerships forged with private sector hospitals which enabled IR to maintain access to important treatments such as tumour ablation and uterine fibroid and

prostate artery embolization in “low-risk” environments. In parallel, comprehensive cover was provided at “hot” sites for the spectrum of COVID and nonCOVID emergencies like embolization, thrombectomy, complex venous access, and percutaneous drainage of obstructed kidneys, bile ducts, and abscesses.2 Published activity data bear this out and have shown that the reduction in IR activity during the first wave of lockdown, by 41% and 25% in outpatient and inpatient volumes respectively, was far less than that seen in other procedurecentred specialties like vascular surgery, urology, and endoscopy.3 Even prior to the pandemic, it was estimated that approximately one in 10 in-patients were treated by IR during their hospital stay, underlining the key importance of IR in the day-today functioning of hospitals.4 Formal incorporation of IR treatments into patient pathways and access to IR expertise through ward rounds and clinics would allow far more efficient and streamlined care for those requiring it.

Across the spectrum of clinical practice, minimally invasive IR treatments result in quicker recovery, lower morbidity, and shorter hospital stays. Crucially in these times, these procedures can often be performed in a day case or ambulatory care unit. The availability of such units can hugely support emergency preparedness plans. This was illustrated in the first wave of the pandemic, when

Even prior to the pandemic, it was estimated that approximately one in 10 in-patients were treated by IR during their hospital stay, underlining the key importance of IR in the day-today functioning of hospitals.” most endoscopy services ceased and IR stepped in to perform many more radiologically inserted gastrostomies rather than percutaneous endoscopic gastrostomies.

An additional benefit of high-volume IR day case units is the efficient utilisation of resources and an increase in financial income for the organisation.

Increasingly, organisations within the UK have come to recognise these clinical and financial benefits, and many centres have invested in such facilities. However, these are not universally available, as highlighted in the recently published Radiology GIRFT [Get It Right First Time] report.5 Alongside this, there is a need for robust workforce planning to ensure there are adequate numbers of IR doctors, nurses, radiographers, and administrative staff to sustain IR services.

The skillset that IR staff possess is extremely versatile, and there were many reports of IR supporting the frontline response during the first wave of the pandemic. This included redeploying staff in the critical care setting with the goal of providing bed-side procedures

like difficult venous access and ultrasound guided drainage procedures.

Whilst the months ahead will be challenging, there is an opportunity to establish IR practice firmly at the very core of clinical practice through proactive planning and delivery of innovative, effective, and safe care for the benefit of our patients.

I would like to acknowledge the guidance and support from Ian McCafferty (president, British Society of Interventional Radiology [BSIR]) in the preparation of this article.

Stay safe everyone.

Narayan Karunanithy is a member of the Communications Committee, British Society of Interventional Radiology, and is a consultant interventional radiologist at Guy’s & St Thomas’ NHS Foundation Trust, London, UK. References 1. Institute for Healthcare Improvement Triple Aim Initiative, http://www.ihi.org/Engage/Initiatives/ TripleAim/Pages/default.aspx 2. Pendower L, Benedetti G, Breen K, Karunanithy N. Catheter-directed thrombolysis to treat acute pulmonary thrombosis in a patient with COVID-19 pneumonia. BMJ Case Rep. 2020 Aug 11;13(8):e237046 3. Hashmi A, Parikh K, Al-Natour M et al. Interventional radiology procedural volume changes during COVID-19 initial phase: A tertiary level Midwest health system experience. Clin Imaging. 2020 Nov 10;72:31–36 4. Shah SS, Tennakoon L, O’Beirne E, Staudenmayer KL, Kothary N. The Economic Footprint of Interventional Radiology in the United States: Implications for Systems Development. J Am Coll Radiol. 2020 Sep 9:S1546– 1440(20)30873–5 5. Halliday K, Maskell G. Radiology: GIRFT Programme National Specialty Report. Nov 2020. https:// www.gettingitrightfirsttime.co.uk/wp-content/ uploads/2020/11/GIRFT-radiology-report.pdf 6. Rubin C, McCafferty I, Bell J. Provision of Interventional Radiology Services, 2nd ed.

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March 2021 | Issue 81

36 Medical ethics

Thinking about ethics during the COVID-19 pandemic: Insights and practical approaches for interventional radiologists Michelle Shnayder-Adams Eric J Keller Mina S Makary Comment & Analysis “Practicing ethical inquiry and reflection may mitigate the moral distress that can arise from ethical dilemmas,” write Michelle Shnayder-Adams, Eric J Keller, and Mina S Makary—and there have certainly been a number of emotionally-challenging ethical dilemmas for healthcare providers treating patients against the backdrop of the COVID-19 pandemic. The authors discuss the intersection of medical ethics and interventional radiology (IR) amidst this crisis, and propose a framework interventionalists can use to enable decision-making when faced with multiple, conflicting moral obligations, which they say can cause stress and uncertainty.

I

n stressful times, challenges associated with making ethical and honourable decisions become more apparent. The COVID-19 pandemic has placed an immense amount of strain on the medical community, and interventional radiologists are not exempt from this pressure. When ethical norms are disrupted, we have an even greater responsibility as a specialty to bring ethical decision-making to the forefront.

This article will highlight: 1) how ethics and IR intersect, 2) how ethical issues have been heightened during the COVID-19 pandemic, and 3) how to apply a framework to ethical decisions pertaining to IR care.

How ethics and IR intersect

The discipline of ethics helps us to decide how we ought to behave as a standard of behaviour.1 To some, it may not seem obvious to discuss and practice ethical decision-making in medicine as it appears innate. After all, physicians pledge the Hippocratic Oath and vow to “do no harm”.

However, conflict arises when ethical principles clash. The COVID-19 pandemic has challenged a number of ethical values, including duty to care, equity, autonomy, and individual liberty.

As we continue to practice in a new

recognise an ethical dilemma societal norm filled with personal risk, limited resources, and limited physical contact, we must continue to reflect on our ideals and ethical identities during patient care delivery.

Many professional societies, including the Society of Interventional Radiology (SIR), have created Codes of Ethics, which offer guiding principles for IR physicians on societal ethical expectations.2 Respect for human dignity, respect for human rights, and respect for the law are all included. However, these guidelines are not always sufficient when faced with practical matters. Are you obligated to place a central venous catheter in a patient with COVID-19 at a time when personal protective equipment is limited, and other departments have the means to perform this service?

COVID-19 has heightened the ethical issues facing interventional radiologists

Some may argue that a pandemic qualifies as a state of emergency in which physicians must act on the best interest of society. However, in practice, it is much

more challenging to jeopardise your own health and the health of your family and colleagues for the sake of professional duty. Physicians have a responsibility to care for patients, but this responsibility must be balanced with a duty to one’s health and one’s family.3,4 We must also resist the urge to deflect risk onto others and should view patient care as a collective responsibility. With thoughtful reflection and support from institutions to ease the moral burden of these difficult choices, IR physicians can weigh their competing responsibilities and come to a solution that balances all the ethical and practical issues at play.5 With the development of the COVID-19 vaccine, resource allocation concerns have shifted from intensive care unit (ICU) bed provision to vaccination distribution priority. How do we decide on a fair system of vaccine distribution?

Whether you are a healthcare leader responsible for the development of a vaccine rollout plan or a frustrated IR practitioner awaiting a vaccine, resource allocation and equity affects all healthcare providers. The Center for Disease Control (CDC) has advocated to minimise morbidity and mortality and preserve societal functions.6 With these priorities in mind, some vaccination algorithms have prioritised age over exposure frequency. Without transparency from leaders about their chosen ethical approach, it is reasonable for younger practitioners with frequent exposures to feel betrayed when they observe vaccine prioritisation of older practitioners with lesser patient interaction. There is no absolute right answer when it comes to prioritisation in the setting of scarce resources, but as these ethical dilemmas unfold, it is crucial for healthcare leaders to maintain transparency and robust discussion with their communities to reach more optimal solutions.

Imagine you are running a busy consult service and you are tasked with acquiring

gather relevant information from all parties involved

consent for a gastrostomy tube placement in a non-English speaking patient with COVID-19 who has been delirious the last few nights. Her son is her power of attorney. Would you risk exposure, call a translator, and attempt to assess the patient’s decision-making capacity, or just call the patient’s son to get consent?

From an ethical standpoint, many IR physicians may agree that they would

Issue 81 | March 2021 advocate for explaining the procedure and its risks to the patient despite the extra risk, time, and logistic challenges.

From a practical standpoint, respecting a patient’s autonomy, while paramount, can be often inconvenient, especially during a pandemic. Despite the challenges, we must keep in mind that assessing a patient’s decision-making capacity is one of our responsibilities as IR physicians, and if needed, there are resources and other departments in the hospital to help with capacity assessments.

Despite being accountable to our individual patients, IR physicians also have a responsibility to the general public. These two obligations may lead to internal turmoil and conflict. Visitor restrictions limit disease exposure for patients, providers, and hospital staff but at the expense of some individual liberty.

Limiting a patient’s number of visitors may support a public effort to reduce spread of disease, but the social isolation of patients can lead to psychological distress and worse patient outcomes.7–9 New challenges arise as social distancing and isolation have become the standard for safety. Evidence supports the protective benefits of social connections and support during pregnancy and labour; there are increased maternal, fetal, and

scrutinise possible options using various ethical theories

pregnancy risks when pregnant and laboring women lack support. As health care professionals take appropriate precautions to protect patients and themselves from infection, there must be a balance to ensure that we do not neglect the importance of social and emotional support during important milestones such as pregnancy and childbirth. Resources are available to help pregnant women, and technology represents an opportunity for innovation in providing care.

In balancing these opposing priorities and accepting the restriction of some individual liberties for the betterment of society, interventional radiologists may find that going beyond their usual levels of communication with patients and families may be necessary to preserve the patient-doctor-family relationship during a pandemic.

Pandemic planning

The COVID-19 pandemic has forced medical professionals, including interventional radiologists, to deal with ethically-ambivalent decisions every day.

Many frameworks have been developed

Medical ethics 37

Good pandemic planning requires reflection on values, because science alone cannot tell us how to prepare for a public health crisis.” to aid in the ethical decision-making process.1,5,10–121,21 Planning for the next pandemic influenza outbreak is underway in hospitals across the world. The global SARS [severe acute respiratory syndrome] experience has taught us that ethical frameworks to guide decision-making may help to reduce collateral damage and increase trust and solidarity within and between health care organisations. Good pandemic planning requires reflection on values, because science alone cannot tell us how to prepare for a public health crisis.

Here, we present an ethical framework for pandemic influenza planning. The ethical framework was developed with expertise from clinical, organisational, and public health ethics and validated through a stakeholder engagement process. The ethical framework includes both substantive and procedural elements for ethical pandemic influenza planning.

The incorporation of ethics into pandemic planning can be helped by senior hospital administrators sponsoring its use, by having stakeholders vet the framework, and by designing or identifying decision review processes. We discuss the merits and limits of an applied

decide how to act ethical framework for hospital decisionmaking, as well as the robustness of the framework. The need for reflection on the ethical issues raised by the spectre of a pandemic influenza outbreak is great. Our efforts to address the normative aspects of pandemic planning in hospitals have generated interest from other hospitals and from the governmental sector. The framework will require re-evaluation and

refinement and we hope that this paper will generate feedback on how to make it even more robust.

The framework for ethical decision-making in IR: Our proposal

One such approach is as follows: 1) recognise an ethical dilemma, 2) gather relevant information from all parties involved, 3) scrutinise possible options using various ethical theories, 4) decide how to act, and 5) reflect on the outcome.

For example, this framework may be applied to triaging patients. First, we recognise that triaging with limited resources is an ethical issue. Second, we may gather information about the acuity of all patients involved and consider occupancy capacity at nearby facilities.

Third, question the correct course of action under a utilitarian, rights, justice, common good, and virtue approach. For instance, under the justice approach, consider which options treats people equally—making sure not to succumb to bias and favouritism. Fourth, decide which patient to treat, and, fifth, consider how your decision impacted those involved. Practicing ethical inquiry and reflection may mitigate the moral distress

reflect on the outcome

that can arise from ethical dilemmas.13 Interventional radiologists have started to recognise the importance of ethical discussion in our field. SIR and the Society of Interventional Oncology (SIO) have created committees on applied ethics, and we have a growing body of literature on ethical topics in IR including: complications,14 conflicts of interest,15 research ethics,16 and futility.17–19 The underrepresentation of clinical ethics in IR could be due to the way by which it is often presented, because it is frequently viewed in terms of abstract principles and sensational cases rather than how it applies to interventional radiologists’ daily practice.

Despite its relative under recognition, ethics is important to all professional groups; it is the collective values that guide our behaviours and allow us to resolve challenging situations that are common in health care.

Informed consent in health care is widely accepted and expected both ethically and legally, but its complexity

is often taken for granted. 1,2 The COVID-19 pandemic has highlighted the need for these discussions, and we must continue to provide platforms to discuss how best to act in ethically in challenging situations.

Michelle M Shnayder-Adams is an interventional radiology resident at the University of Michigan Hospital, Ann Arbor, USA. @MMShnayderMD on Twitter.

Eric J Keller is an interventional radiology resident at the Stanford University Medical Center, Stanford, USA. @IR_Ethics on Twitter.

Mina S Makary is an assistant professor, interventional radiologist, and the director of scholarly activity and research at the Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, USA. @MinaMakaryMD on Twitter.

References 1. Markkula Center for Applied Ethics. Accessed January 21, 2021. https://www.scu.edu/ethics/ 2. SIR Code of Ethics. Published online 2018. Accessed June 21, 2020. https://www.sirweb.org/globalassets/ aasociety-of-interventional-radiology-home-page/ about-us/governance/sir-code-of-ethics_approvednovember-2018.pdf 3. Shnayder MM, Keller EJ, Makary MS. COVID-19 Ethics: What Interventional Radiologists Need to Know. J Vasc Interv Radiol. 2020;31(10):1720-1723. doi:10.1016/j. jvir.2020.07.003 4. Bakewell F, Pauls MA, Migneault D. Ethical considerations of the duty to care and physician safety in the COVID-19 pandemic. Cjem.:1-4. doi:10.1017/ cem.2020.376 5. Thompson AK, Faith K, Gibson JL, Upshur RE. Pandemic influenza preparedness: an ethical framework to guide decision-making. BMC Med Ethics.

2006;7(1):1-11. doi:10.1186/1472-6939-7-12 6. CDC. COVID-19 and Your Health. Centers for Disease Control and Prevention. Published February 11, 2020.

Accessed January 21, 2021. https://www.cdc.gov/ coronavirus/2019-ncov/vaccines/recommendations. html 7. Jago CA, Singh SS, Moretti F. Coronavirus Disease 2019 (COVID-19) and Pregnancy: Combating Isolation to Improve Outcomes. Obstet Gynecol. 2020;136(1):3336. doi:10.1097/AOG.0000000000003946 8. Abad C, Fearday A, Safdar N. Adverse effects of isolation in hospitalised patients: a systematic review.

J Hosp Infect. 2010;76(2):97-102. doi:10.1016/j. jhin.2010.04.027 9. Hao F, Tam W, Hu X, et al. A quantitative and qualitative study on the neuropsychiatric sequelae of acutely ill COVID-19 inpatients in isolation facilities. Transl Psychiatry. 2020;10(1):1-14. doi:10.1038/s41398-02001039-2 10. Berlinger N, Wynia M, Powell T, et al. Ethical framework for health care institutions responding to novel Coronavirus SARS-CoV-2 (COVID-19) guidelines for institutional ethics services responding to COVID-19. Safeguarding Communities Guid Pract.

2020;2.

11. A Framework for Making Ethical Decisions | Science and Technology Studies. Accessed January 21, 2021. https://www.brown.edu/academics/scienceand-technology-studies/framework-making-ethicaldecisions 12. Ethical Framework for Health Care Institutions & Guidelines for Institutional Ethics Services Responding to the Coronavirus Pandemic. The Hastings Center. Accessed June 18, 2020. https://www. thehastingscenter.org/ethicalframeworkcovid19/ 13. Rushton CH, Kaszniak AW, Halifax JS. Addressing Moral Distress: Application of a Framework to Palliative Care Practice. :9.

14. Keller EJ. Reflect and Remember: The Ethics of Complications in Interventional Radiology.

Semin Interv Radiol. 2019;36(2):104-107. doi:10.1055/s-0039-1688423 15. Clark JM, Anderson D, Makary MS, Keller EJ. Understanding Bias: A Look at Conflicts of Interest in IR. J Vasc Interv Radiol. 2019;30(5):765-766. doi:10.1016/j.jvir.2019.01.002 16. Bozorghadad S, Newton IG, Perez AW, Makary MS, Keller EJ. Research Ethics in IR: The Intersection Between Care and Progress. J Vasc Interv Radiol.

2020;31(5):846-848. doi:10.1016/j.jvir.2020.02.014 17. Clark JM, Keller EJ. Reconsidering Requests—Futility in IR. J Vasc Interv Radiol. 2019;30(6):961-962. doi:10.1016/j.jvir.2019.01.025 18. Keller EJ, Perez AW, Makary MS. Informed Consent: Beating a Dead Horse or an Opportunity for Quality Improvement? J Vasc Interv Radiol. 2020;31(1):139140. doi:10.1016/j.jvir.2019.08.010 19. Keller EJ, Rabei R, Heller M, Kothary N. Perceptions of Futility in Interventional Radiology: A Multipractice Systematic Qualitative Analysis. Cardiovasc Intervent Radiol. 2021;44(1):127-133. doi:10.1007/s00270-02002675-3

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Days to First Reintervention in the Lutonix AV IDE Trial*

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* Lutonix™ AV Clinical Trial data on file. N=285. At 6 months, treatment with Lutonix™ 035 AV DCB resulted in a primary patency rate of 71.4% versus 63.0% with PTA alone. Primary patency defined as ending with a clinically driven re-intervention of the target lesion or access thrombosis. The primary effectiveness analysis for superiority of DCB vs. PTA was not met with a one sided p-value of p = 0.0562. Mean time to TLPP event for subjects with an event was longer for DCBs (321.8 vs. 207.4 d; p< .0001). Percentages reported are derived from Kaplan-Meier analyses. Lutonix Global AV Registry data on file. N=320. At 6 months, treatment with Lutonix™ 035 DCB resulted in a target lesion primary patency (TLPP) rate of 73.9%. Lutonix Global AV Registry on file. N=320. By access type, treatment with Lutonix™ 035 DCB resulted in a TLPP of 78.1% for native fistulas only (240/320) and 61.9% for synthetic (graft) only (80/320). TLPP defined as the interval following index procedure intervention until clinically driven reintervention of the target lesion or access thrombosis. Percentages reported are estimated based on Kaplan-Meier estimates.

The Lutonix™ 035 Drug Coated Balloon PTA Catheter is indicated for percutaneous transluminal angioplasty (PTA), after pre-dilatation, for treatment of stenotic lesions of dysfunctional native arteriovenous dialysis fistulae that are 4 mm to 12 mm in diameter and up to 80 mm in length. Please consult product labels and instructions for indications, contraindications, hazards, warnings, and precautions.

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© 2021 BD. BD, the BD Logo, and Lutonix are trademarks of Becton, Dickinson and Company or an affiliate. Illustrations by Mike Austin. Copyright 2021. All Rights Reserved. BD-16426

Issue 81 | March 2021

Access to IR 39

GIRFT Radiology report calls for expansion of IR day-case capacity in the UK The Royal College of Radiologists (RCR) has welcomed the Getting It Right First Time (GIRFT) report into imaging services in England, released 10 November. One of the key recommendations of the report is for radiology departments to have dedicated provision of interventional radiology (IR) facilities.

T

he GIRFT radiology team, led by consultant radiologist Katharine ‘Kath’ Halliday (Nottingham University Hospitals NHS Trust, Nottingham, UK), and supported by RCR past-president Giles Maskell (Royal Cornwall Hospitals NHS Trust, Truro, UK) and radiology service experts Elaine Quick (Salford Royal NHS Foundation Trust, Salford, UK) and Lucy Beeley (Mid Yorkshire Hospitals NHS Trust, Wakefield, UK), spent more than two years investigating variation across National Health Service (NHS) imaging services, analysing data and visiting hundreds of hospital radiology departments. The team also consulted with the RCR and the wider radiology community.

The primary stated aim of the GIRFT radiology national specialty report is to make radiology services more patient-centric and accessible. Major themes include the need for standardised, streamlined radiology pathways and systems, and efficiencies in workload and workforce management.

The report covers the impact of COVID-19 on services and builds on issues highlighted in previous radiology investigations, such as the Care Quality Commission’s 2018 Radiology Review and a recent article entitled “Diagnostics: Recovery and Renewal”, as well as various RCR publications.

Key patient-focussed recommendations include the ongoing creation of community-based diagnostic hubs recently promised by NHS England/Improvement (NHSE/I), online booking and extended hours to suit outpatient appointments, and dedicated provision of IR facilities.

The GIRFT team’s remit was to identify how imaging services can reduce variation and look to free up capacity and maximise existing resources.

However, the report authors emphasise that NHS imaging cannot provide the best possible service for patients or clinicians without more staff and resources.

They state: “Unless there is investment in increasing staff numbers overall, it will not be possible to provide the quality of service that patients expect, that other departments require, and that radiology teams wish to deliver.”

Welcoming the report’s publication, RCR vice president for clinical radiology William Ramsden (Leeds Children’s Hospital, Leeds, UK) says: “The GIRFT report is truly comprehensive, clearly stating the pivotal role of imaging in patient care, alongside the complex and significant pressures facing departments, and making positive recommendations to improve diagnostic and IR provision across England.

“As well as backing the RCR’s calls for increased investment in departmental space, equipment, and staffing, and the ongoing creation of imaging networks, the authors detail insightful suggestions for optimising imaging pathways and the use of resources and data. All of this will make NHS radiology more patient-focussed, accessible, and efficient, and we strongly endorse the team’s recommendations.”

The report makes 20 headline recommendations, with more than 50 supporting actions to be undertaken by trusts, the GIRFT team, NHSE/I, the RCR, and imaging community stakeholders.

Short-term and ongoing GIRFT recommendations include:

The creation of imaging networks, in line with NHSE/I’s target of 18 nation-wide networks by 2035 Imaging community stakeholders to continue ongoing work to review NHS coding for diagnostic and interventional radiology and end multiple NHS data submissions National targets for time from imaging test-to-report, to be progressed by trusts and NHSE/I over the next six months All radiology services to work towards providing dedicated facilities for IR day-case patients, with further guidance from GIRFT due in the next 12 months

Medium- and long-term recommendations include:

under-resourced, we know IR expertise saves lives and saves the NHS money. We particularly applaud the GIRFT team’s moves to boost recognition of IR via calls to expand IR day-case capacity on a national scale and improve monitoring.

“We agree there is scope to maximise existing diagnostic and interventional capacity through improved oversight and understanding of radiologists’ workloads, as well as enabling appropriate role extension for allied health professionals. We have started project work on those recommendation areas, alongside the SoR and other stakeholders. Trusts must also take seriously the report’s recommendation to assess workforce needs, and the RCR can help services here by sharing our comprehensive radiologist census data.

“However, given the ongoing crisis in imaging department staffing, we must again stress that these efficiency solutions will still only take us so far without the substantial workforce increases that NHS radiology desperately needs.

“On reporting targets, we previously welcomed the premise of national standards for the reporting of imaging, stating targets could be phased in to help benchmarking, and we appreciate GIRFT supporting a soft approach to any implementation.

“We are pleased to see GIRFT recommend standardised radiology IT solutions and the use of

National protocols for imaging common conditions, to be progressed by GIRFT, the RCR, and the Society of Radiographers (SoR) over the next 18 months Standard definitions and expected productivity for radiologists, to be progressed by the RCR over the next 18 months Reporting standards for radiographers and radiology trainees, to be progressed by the RCR and SoR over the next 18 months NHSE/I to create real-time demand management tools for diagnostic and interventional workflows, over the next two years Commenting further on the GIRFT recommendations, Ramsden adds: “Despite being

Katharine Halliday (L), with, from top to bottom: Giles Maskell, Elaine Quick, and Lucy Beeley

Unless there is investment in increasing staff numbers overall, it will not be possible to provide the quality of service that patients expect, that other departments require, and that radiology teams wish to deliver.”

referral software. These are ‘quick win’ systematic improvements for helping to manage demand and have long been championed by the RCR. The suggested creation of real-time workflow management dashboards for both diagnostic and IR activities also has exciting potential.

“There are already many inspirational examples of local service innovation, as demonstrated by the host of departmental case studies featured throughout the GIRFT report, and the community as a whole is engaging with national initiatives such as the creation of imaging networks and guiding artificial intelligence tools in development.

“It is now essential that NHS leaders and providers engage with the GIRFT radiology programme as it progresses, supporting radiology teams to upskill, adapt and adopt best practice.

“The recommendations are ambitious but achievable, and we look forward to working with the GIRFT team, trusts, and other national bodies to see them realised.”

Issue 81 | March 2021

Market watch 41

Clinical News

Beau Toskich and Aiwu Ruth He

New trial launches investigating combination therapy of radioembolization and immunotherapy in HCC patients

The Society of Interventional Oncology (SIO) and Boston Scientific have announced a new multicentre, prospective, randomised trial to study combination therapy of radioembolization and immunotherapy in early and intermediate hepatocellular carcinoma (HCC) patients not eligible for curative treatments: ROWAN. Led by investigators Beau Toskich (Mayo Clinic Florida, Jacksonville, USA) and Aiwu Ruth He (Georgetown University Lombardi Comprehensive Cancer Center, Washington, DC, USA), ROWAN will evaluate the safety and efficacy of TheraSphere Y-90 glass microspheres (Boston Scientific) administered before initiation of durvalumab with tremelimumab compared to treatment of TheraSPhere alone. The study will assess local tumour control, progression-free survival, and the effect of TheraSphere radiation dosimetry on immune response.

New embolic device used in interventional oncology for highly targeted tumour treatment

A novel embolization device in the interventional oncology space—the GPX embolic device (Fluidx Medical Technology)—has successfully been used in a patient to therapeutically devascularise a tumour for the first time.

“We are impressed with the GPX embolic,” comments Andrew Holden (Auckland City Hospital, Auckland, New Zealand). “We delivered GPX through a long 150cm 2.4F (0.022inch inner diameter) microcatheter from the patient’s radial artery. GPX was easy to use, precise, and occluded the tumour well. We look forward to using GPX across a broad range of applications to improve patient care.”

The GPX embolic device is an innovative embolic designed to combine the benefits of other embolics like coils, particles, and liquids with simplified preparation, delivery, precision, and control leading to durable, long-term occlusions.

The GPX technology is a low viscosity, aqueous-based solution in a syringe that solidifies into a durable embolic material upon delivery, without

polymerisation or dimethyl-sulfoxide (DMSO) precipitation associated with other embolics.

According to a company press release, GPX is packaged ready-to-use in a syringe, requires less than one minute of tableside preparation by the clinician, and may be delivered through standard catheters or microcatheters.

“GPX is easy to prepare, deliver, and control,” says Ryan O’Hara (University of Utah, Salt Lake City, USA). “GPX is responsive to the physician and layers well in the vessel during delivery, resulting in improved targeting and control. I see potential for this embolic in IO and other peripheral vascular and neurovascular uses.”

Therapeutic, super-selective embolization is a high-growth procedure used for minimally invasive, targeted treatment of internal bleeds, tumours, aneurysms, vascular malformations, uterine fibroids, varicose veins, and other uses. A variety of embolic devices (coils, particles, plugs, liquids) are used for these procedures; however, many can have issues in terms of ease of use, and controlled, consistent delivery. Some embolics also require specialised catheters and solutions as well as complex and lengthy preparation processes.

31.4% were chronic total occlusions.

At six and 12 months, the authors report that freedom from clinicallydriven target lesion revascularisation was 95.5% and 88.7% and the primary patency rates were 88.7% and 82.3%, respectively.

At 12 months, significant improvements were noted in Rutherford categories and ankle-brachial indices, and in multiple regression analyses, both diabetes mellitus and no distal run-off vessel showed a trend toward worse target lesion revascularisation, while other factors such as drug-coated balloon predilection or the lesion length were not predictive.

ISABELLA trial for the treatment of failing AV fistulas in haemodialysis patients completes enrolment

MedAlliance has announced completion of patient enrolment in the ISABELLA clinical trial with the Selution SLR 018 drug-eluting balloon (DEB) for the treatment of dysfunctional arteriovenous (AV) fistulas in end-stage renal failure patients undergoing haemodialysis.

Selution SLR (sustained limus release) is a novel sirolimus-eluting balloon that provides a controlled sustained release of drug, similar to a drug-eluting stent (DES).

Twelve-month LOCOMOTIVE EXTENDED results “promising”

B Braun has revealed that 12-month results from the LOCOMOTIVE EXTENDED study of the company’s Multi-Loc multiple stent delivery system have been published in Vasa: European Journal of Medicine. The study authors, Klaus Amendt (Diakonissenkrankenhaus Mannheim, Mannheim, Germany) and colleagues conclude that the Multi-Loc “provides promising results concerning target lesions revascularisation and primary patency at 12 months”.

They add that use of the Multi-Loc stent system is both safe and effective for provisional repair of flow-limiting dissections or recoil following plain balloon angioplasty and drugcoated balloon angioplasty of the femoropopliteal artery.

The LOCOMOTIVE EXTENDED (Multi-Loc for flow-limiting outcomes after plain old balloon angioplasty and/or drug-coated balloon treatment in the infrainguinal position with the objective to implant multiple stent segments) study is a prospective, single-arm, multicentre observational study, in which B Braun’s Multi-Loc multiple stent delivery system was used for provisional stenting of the femoropopliteal artery.

Amendt et al enrolled 357 patients with 449 femoropopliteal lesions and a mean age of 71±10 years. The mean lesion length was 16±9.7cm; 44.5% of which were TASC II C/D lesions and

Multi-Loc

ControlRad Select

ISABELLA (Intervention with Selution SLR agent balloon for endovascular latent limus therapy for failing AV fistulas) is a prospective, single-centre, multi-investigator, nonblinded, single-arm trial investigating the safety and feasibility of the Selution SLR 018 DEB for the treatment of failing AV fistulas in 40 haemodialysis patients.

The objective of this study is to

determine the safety and efficacy of the Selution SLR 018 DEB in the treatment of dysfunctional AV fistulas in endstage renal failure patients undergoing haemodialysis.

The efficacy endpoint of interest is six-month target lesion primary patency and the safety endpoint is freedom from localised or systemic serious adverse events through 30 days that reasonably suggest the involvement of the AV fistula circuit.

ControlRad Select imaging system gains FDA market clearance

ControlRad has announced US Food and Drug Administration (FDA) 510(k) clearance to market ControlRad Select, a technology that utilises proprietary semi-transparent filters, a user-interface tablet, and image processing algorithms to reduce radiation exposure during fluoroscopically guided procedures.

The technology is retrofitted onto customers’ existing Siemens Artis zee interventional imaging systems. In preparation for the commercialisation efforts, ControlRad has entered into an exclusive agreement with Boston Scientific to sell the ControlRad Select technology.

“With the FDA clearance and the reach of the global medical device sales team, every cath [catheterisation], EP [electrophysiology], and IR [interventional radiology] lab in the country that has a Siemens Artis zee will now have the opportunity to reduce their radiation dose by 85%1 without compromising image quality,” stated Guillaume Bailliard, CEO of ControlRad. “The health risks to the medical staff due to lifetime radiation exposure in cath labs have been well documented, including increased incidence of cataracts, atherosclerosis and even left-brain tumours,” stated Simon Dixon, chief of cardiology at Beaumont Hospital, Royal Oak, USA. “We recently completed a clinical trial designed to evaluate how this novel technology might reduce radiation exposure in the cath lab. I have long been passionate about finding innovative ways to improve safety for my colleagues in the lab while they are performing lifesaving procedures for our patients.”

Issue 81 | March 2021

Market watch 43

Industry News

CATHIS Smart system

CATHI launches portable endovascular simulator system to med tech and pharma industries

Endovascular stimulator company CATHI has launched a campaign promoting CATHIS Smart, its portable system, to medical technology and pharmaceutical companies. The system displays all types of endovascular intervention in any medical field, and is designed for neuroradiology, cardiology, radiology, angiology, and pneumology training.

CATHIS Smart is the size of a laptop, and can be customised to individual user needs, such as being set up with specific devices or instruments.

According to CATHI, the system enables sales teams to give “simplified yet high-definition demonstrations of complex products to their customers”.

Their company press release states that sales teams can “quickly learn simpleto-follow step-by-step procedures to gain a basic understanding of vessel anatomy, plus the handling of instruments or devices”. CATHIS Smart can also be used by engineers as a tool for aiding product design by facilitating visualisation and the extrapolation of ideas, as well as factoring in ease of operation and a positive user experience.

Users of CATHIS Smart can jump directly to specific steps within the workflow, which the company say is useful for educational purposes.

“Simulators are essential items of equipment for the cath lab, both for initial training and maintaining vital skills,” says Andreas Götte, head of Cardiology at the St Vincenz Hospital, Paderborn, Germany. “But to be effective they must resemble ‘real life’ clinical practice: we must see the coronary artery as it really is, being able to manipulate guide wires as well as catheters and balloons.”

The CATHIS Smart simulator is supported by a range of hardware including a control unit, notebook, and foot pedal.

Biomodex announce partnership to develop Evias Plus

Biomodex has announced its partnership with two of the top medical centres in France and a health system in the USA to develop Evias Plus, a training solution for treatment of ischaemic stroke.

“Thrombectomies are very complex in nature and carry a high risk of

complications. What is more, these procedures continue to evolve, given the development of new devices and approaches, requiring neuroradiologists to continually advance their skills,” says Francois Eugene, interventional neuroradiologist at the Centre Hospitalier Universitaire, Rennes, France, a partnering medical centre.

Anthony Le Bras, also an interventional neuroradiologist at the Centre Hospitalier Universitaire, Rennes, France, adds, “Biomodex’s solution will not only enable physicians to stay up-to-date, but will also accelerate training of fellows to help ensure we have enough physicians to support this rapidly expanding field.”

According to the company, Evias Plus offers an innovative approach for physician training, particularly fellowship programmes. Biomodex adds that the solution for ischaemic stroke enables neurointerventionalists to simulate fluoroscopy-guided procedures in a real-life catheterisation laboratory environment. The company reports that

EVIAS Plus Top view

the models come with several realistic, 3D-printed blood vessel models or cartridges that plug into a station that simulates systemic flow using Biomodex Bloodsim to replicate blood density and viscosity. Other key features include: A bio-based clot, injection system and distal filter for clot collection/ validation of retrieval Femoral access and adjustable aortic arch Customised tissue-like patient-specific aortic arches, including right and left radial and femoral access accessories “Mechanical thrombectomy (MT) has revolutionised the neurological outcome of acute ischaemic stroke patients.

Nonetheless, still a large proportion of eligible patients are not treated with MT because of a lack of physicians trained to perform this procedure in an emergency.

“We therefore have an urgent need to train more physicians to offer this treatment to more patients. This new simulation solution offers highly realistic navigation sensations with the possibility to switch within minutes from one anatomy to another,” says Raphael Blanc, co-chief interventional neuroradiologist at the Fondation Adolphe de Rothschild, Paris, France.

“Biomodex’s advanced training system is a significant improvement over traditional training approaches

because the models are incredibly realistic and allow us to gain handson training for the manipulation of catheters under fluoroscopy. We can also practice navigating realistic aortic arch anatomies ranging from common to complex,” comments Ajay Wakhloo, chief of interventional radiology at Beth Israel Lahey Health, Boston, USA.

Cardiovascular Systems and Chansu Vascular Technologies partner to develop new everolimus DCBs

Cardiovascular Systems (CSI) has partnered with Chansu Vascular Technologies (CVT) to develop novel peripheral and coronary everolimus drug-coated balloons (DCBs).

Under the terms of the agreements, CSI will provide milestone-based financing to CVT for the development of the DCBs. Under an acquisition option agreement, upon CVT’s completion of key technical and clinical milestones in the development programme, CSI will have exclusive rights and obligations to acquire CVT, subject to the satisfaction of closing conditions set forth in the agreement.

CVT, which is based in Sunnyvale, USA, develops peripheral and coronary DCBs using everolimus.

“The CVT DCBs will be designed to capitalise on the proven long-standing anti-restenotic benefits of everolimus for the treatment of patients with cardiovascular lesions,” comments CVT founder Philippe Marco in the company’s announcement. “This collaboration enables us to develop a new class of DCBs that we believe will improve patient outcomes.”

Ryan Egeland, chief medical officer of CSI, states: “This partnership is consistent with our strategic vision to develop an innovative portfolio of new products. We believe these nextgeneration DCBs will complement our current and growing portfolio of products for the treatment of complex coronary and peripheral disease. We are thrilled to be working with CVT in this partnership and are extremely confident that [Philippe] Marco and his team’s extensive past DCB experience will prove invaluable in developing these next-generation DCBs.”

makes it easier for overseas doctors to register with the General Medical Council.

Currently, many Indian candidates travel to the UK or to centres in Hong Kong and Singapore to access the exam.

The new venue, which is currently being adapted and equipped with exam stations, is based in the south Indian city of Hyderabad.

Initially, it will host the Final FRCR Part B exam, before rolling out the First FRCR and Final FRCR Part A elements.

Capacity will be subject to logistics and scaled up as the centre becomes established. However, the ARI Academy hopes to hold sittings for up to 150 candidates in future.

The RCR and ARI Academy had hoped to host the first Hyderabad exams in spring 2021; however, timelines are now under ongoing review due to the knock on impact of COVID-19 restrictions and logistical challenges.

Welcoming news of the joint agreement to launch the exam centre, RCR Overseas Ambassador for India Venkat Sudigali says: “It is a great initiative from the RCR to establish overseas exams centre in India.

“This exciting development will be of great benefit to many radiologists in India who are keen to attempt the FRCR exam to add to their qualifications, and also for those who potentially want to work in the UK in future, to learn new skills, and gain experience in the NHS.” The new exam venue builds on recent collaborative work between the RCR and ARI, who worked with education and training partners in 2019 to create a scheme providing three-year placements for Indian radiologists looking to develop their skills working in the UK’s National Health Service (NHS).

Commenting on the Hyderabad exam venue, Sreenivasa Raju Kalidindi, ARI

RCR launches new radiology exam site in India The UK Royal College of Radiologists (RCR) has partnered with the Apollo Radiology International (ARI) Academy to create a new exam centre in India.

The move means radiologists in India and surrounding countries will soon be able to sit RCR Fellowship (FRCR) exams locally, reducing travel and expense for candidates and with the aim of expanding RCR exam capacity across the region.

An RCR press release states that, as the RCR Fellowship is “an internationally recognised benchmark of excellence”, there is high demand for FRCR exams in India. The press release also notes that RCR Fellowship status

CEO and director of the ARI Academy, says: “It is a privilege to partner with the RCR in working towards a common vision of making FRCR exams more accessible and affordable to radiologists in India and other countries in this region.

“This initiative will set new benchmarks and empower large numbers of radiologists with the knowledge required to achieve higher standards in their practice.”

The RCR and ARI will release more information on the official launch of the centre and first exam bookings as soon as possible.

Issue 81 | March 2021

Market watch 45

Product News Soundbite announces Health Canada approval for SoundBite crossing system– Peripheral (14P)

Soundbite Medical Solutions has announced Health Canada approval for the SoundBite Crossing System – Peripheral (SCS-P) with the 0.014” Active Wire (14P).

The SCS-P (14P) is intended for the treatment of patients suffering from peripheral arterial disease (PAD) with heavily calcified above-the-knee (ATK) and below-the-knee (BTK) chronic total occlusions (CTOs).

The SCS-P 14P system comprises the SoundBite Console and the 0.014” SoundBite Active Wire. SCS-P leverages Soundbite’s proprietary method to produce and safely deliver shock waves via guidewire platforms to selectively ‘micro- jackhammer’ through calcified lesions. SBCS-P has CE mark and Health Canada approval in both 0.018” and 0.014’ platforms; the 0.018” platform has also US Food and Drug Administration (FDA) (510k) approval.

New workhorse wire guide in US and Canada now commercially available

The Approach Authority Workhorse microwire guide (Cook Medical) is now commercially available in the USA and Canada.

Designed as an 0.018-inch diameter workhorse wire guide, Approach Authority can be used for multiple purposes in the same procedure.

Luminor DCB

A company press release states that Approach Authority combines “resilient” nitinol tip technology with a hydrophilic coating. This expands the options to physicians placing balloon dilatation catheters during percutaneous transluminal angioplasty (PTA) in peripheral arteries. Physicians can deliver a variety of devices across this wire to offer a broader range of treatment options for patients.

FDA grants breakthrough device designation to PEDRA Xauron real-time tissue perfusion system

The US Food and Drug Administration (FDA) has granted PEDRA Technology a breakthrough device designation for the periprocedural use of the company’s PEDRA Xauron perfusion system in the treatment of critical limb-threatening

ischaemia (CLTI).

CLTI is a severe form of peripheral arterial disease (PAD) that is defined as ischaemic rest pain, tissue loss, or gangrene (tissue death) that develops as a result of chronically poor blood flow to the lower limbs. If left untreated, CLTI can lead to limb amputation or death. The one-year mortality rate of CLTI patients without amputation is 30.3%, and with amputation is 40.4%.

At five-years post-CLTI diagnosis, the mortality rate exceeds 50%, which is worse than most cancers.

The breakthrough devices programme at the FDA aims to provide patients and providers with timely access to medical devices that offer for more effective treatment and diagnosis of severe diseases, including a prioritised review of market approval regulatory submissions.

Paul Hayes, vascular surgeon and CMO of PEDRA Technology, adds: “With the Xauron device, physicians can at last see real-time perfusion changes during an interventional procedure in the angiographic suite. I am excited about building on our early clinical data and demonstrating that Xauron will save patient lives and limbs.”

Mermaid Medical Group reports full commercialisation of the D-Clot HD rotational thrombectomy system

Mermaid Medical Group recently announced US commercial availability of the D-Clot HD rotational thrombectomy system. As of 12 January, the company reports 25 successful human cases.

A multicentre limited market release evaluation demonstrated the system’s ability to restore flow effectively and safely with no reported complications.

The data derives from several institutions where numerous users applied the technology to patients and showed effectiveness across variations in vessel size, access type, and thrombus morphology.

Reflow Medical introduces Spex LP shapeable reinforced support catheter

Reflow Medical introduces the lowprofile Spex LP 0.014 and 0.018-inch reinforced support catheters.

According to the company, the Spex LP is designed with a low-profile tip for accessing and crossing the “tightest and most complex lesions” with a supportive system. The customisable tip can be shaped to the desired angle and is compatible with the physician’s choice of guidewire and procedural technique. The device also features three radiopaque markers that enhance visibility on imaging. Additionally, the Spex LP can be combined with Reflow’s Spex 35 for more robust support, the

company notes.

“Using the new Spex LP with the Spex 35 creates a telescoping action for extra support,” comments S Jay Mathews (Bradenton Cardiology Center, Bradenton, USA), one of the first physicians to use the Spex LP, in the company’s press release.

Jihad A Mustapha (Advanced Cardiac & Vascular Centers for Amputation Prevention, Grand Rapids, USA) adds: “The Spex LP has an extremely low lesion-entry profile and provides unmatched flexibility and trackability, especially in difficult cases.”

FDA approves MicroVention’s lower-profile WEB 17 intrasaccular aneurysm treatment device

of the WEB-IT trial in the Journal of NeuroInterventional Surgery.

MicroVention stated that when placed inside the aneurysm sac, the WEB device’s microbraid technology bridges the aneurysm neck (disrupting blood flow) and creates a scaffold for long-lasting treatment. The WEB system received its first FDA approval in late 2018.

The WEB aneurysm embolization system is indicated for use at the middle cerebral artery bifurcation, internal carotid artery terminus, anterior communicating artery complex, or basilar artery apex for the endovascular treatment of adult patients with saccular, wide neck, bifurcation intracranial aneurysms with dome diameter from 3 to 10mm, and either neck size ≥4 mm or dome-to-neck ratio >1 and <2, advised MicroVention.

Rapid Medical receives FDA clearance for steerable neurovascular guidewire

WEB 17 device

The US Food and Drug Administration (FDA) has granted premarket approval (PMA) for the Woven EndoBridge (WEB) 17 system from MicroVention, a US-based subsidiary of Terumo. This is a new addition to the WEB aneurysm embolization system for the treatment of intracranial wide-neck bifurcation aneurysms.

According to the company, the WEB 17 system is designed with microbraid technology, features a lower-profile delivery system compatible with the Via 17 microcatheter, and includes additional device configurations.

“The excellent clinical results we can achieve with intrasaccular flow disruption technology has changed the way we approach the treatment of wide-neck bifurcation aneurysms, and the WEB 17 system expands upon that,” comments Adam Arthur (Semmes Murphey Neurologic & Spine Institute and the University of Tennessee, Memphis, USA), principal investigator of the WEB-IT pivotal trial. “Now, we can deliver WEB devices using a lowprofile system, similar to those used for standard coil embolization.”

In April 2019, Arthur et al published the final 12-month results

Rapid Medical has announced its Drivewire novel guidewire with a steerable distal top, has received US Food and Drug Administration (FDA) clearance. According to a company press release, Drivewire is the first neurovascular guidewire with a controllable distal end that can change course and shape on-demand for more precise navigation.

Rapid Medical states that, with Drivewire, physicians control the direction and shape of the guidewire’s tip while it is inside the vessel, precisely navigating the neuro and peripheral vasculature. Rapid Medical add that this intravascular steering provides access to difficult anatomical locations, increasing the physician’s ability to treat vascular diseases with less invasive interventional approaches.

The press release states that guidewires are key components for treating intravascular diseases such as ischaemic and haemorrhagic strokes.

Rapid Medical claims that currently physicians do not have direct control over the guidewire tip and often remove the guidewire several times to reshape it before reaching the desired location.

Erez Nossek, (NYU Langone, New York, USA), comments: “The development of Drivewire has been an exciting collaboration. I can now easily navigate through complex anatomies by varying the shape of the wire tip inside the vessel, something that cannot be performed with the current neurovascular guidewires.

“I expect this first-of-its-kind technology to benefit patients with challenging anatomies and increase the interventional treatment options available to them.” Outside of the USA, the device is named Columbus.

UK approves Lipiodol Ultra Fluid for hysterosalpingography in women undergoing infertility workup D-clot HD thrombectomy system

Guerbet has been granted approval for an indication extension in the UK,

March 2021 | Issue 81

46 Market watch

Product News where Lipiodol Ultra Fluid is the only oil-based contrast medium indicated for hysterosalpingography (HSG) in women undergoing infertility workup.

New clinical evidence showing that an HSG with Lipiodol Ultra Fluid enhances pregnancy rates has been recognised by the UK’s Medicines and Healthcare products Regulatory Authority (MHRA).

MHRA’s endorsement of evidencebased clinical practice confirms the benefit of Lipiodol Ultra Fluid in fertility management, a Guerbet press release claims.

One in seven couples face fertility issues in the UK. The fertility workup, during which HSG is performed, is a key step in patient care management.

The technique involves the slow infusion of Lipiodol Ultra Fluid into the uterus, using X-ray monitoring to assess the uterine cavity and tubes.

Women who underwent an HSG with Lipiodol Ultra Fluid had enhanced pregnancy outcomes: In a single centre randomised trial: in a group of women with unexplained infertility or endometriosis who received Lipiodol Ultra Fluid (n=73), twice as many became pregnant

within six months compared to women who did not undergo the procedure (n=85). The pregnancy rate was 38.4% and 16.5%, respectively (p=0.002).

In a multicentre randomised trial: in a group of women who underwent an HSG with Lipiodol Ultra Fluid (n=554), 37% more became pregnant within six months compared to women who received an HSG with a water-based contrast medium (n=554).

The pregnancy rate was 39.7% and 29.1%, respectively (rate ratio [RR]: 1.37 [1.16; 1.61]; p<0.001).

In a meta-analysis of randomised controlled trials: in a group of women who underwent an HSG with Lipiodol Ultra Fluid, 42% more became pregnant within six months compared to women who received a waterbased contrast medium. The overall odds ratio (OR) for pregnancy was significantly in favour of HSG with Lipiodol Ultra Fluid: 1.42 (1.10; 1.85) when compared to HSG with a waterbased contrast medium (six studies; n=2,598).

“Our clinical experience of Lipiodol Ultra Fluid has showed us that its

use is similar to water-based contrast media and does not alter the patient experience during the exam. However, it is noteworthy that long term followup studies showed that performing an HSG with Lipiodol Ultra Fluid reduces the median time to pregnancy by around four months, as compared to an HSG with the reference contrast media,” comments Colin Duncan (Royal Infirmary Edinburgh, Edinburgh, UK; chair of the Society for Reproduction and Fertility).

The UK is the sixth European country to grant approval for HSG in women undergoing infertility workup; it is approved in 10 additional countries.

Medtronic launches IN.PACT AV DCB in Japan for patients undergoing haemodialysis Medtronic has announced the launch of IN.PACT AV drug-coated balloon (DCB) in Japan. IN.PACT AV DCB is indicated for the treatment of obstructive lesions up to 100mm in length in the native arteriovenous (AV) dialysis fistulae in patients with end-stage renal disease (ESRD) undergoing haemodialysis. It is the first DCB to be approved in Japan for this vessel bed.

In Japan, IN.PACT AV DCB received regulatory approval on 23 September 2020 and it became eligible for health insurance reimbursement on 1 February 2021.

According to a press release, IN.PACT AV DCB has the potential to maintain AV access site patency, which can extend the time between reinterventions, therefore maximising a patient’s uninterrupted access to dialysis care has been needed.

In a global clinical trial, patients treated with IN.PACT AV DCB maintained target lesion primary patency longer and required 56% fewer reinterventions to maintain target lesion patency as compared to those treated with standard percutaneous transluminal angioplasty (PTA) through six months.

FDA grants breakthrough device designation for Zenith graft

The Zenith fenestrated+ endovascular graft (ZFEN+) product (Cook Medical) has received breakthrough device designation from the US Food and Drug Administration (FDA).

While the product is not commercially available yet, it will now receive priority review, and Cook will engage in “interactive and timely communication” with the FDA during the clinical trial and premarket review phases. The ZFEN+ is the first product from Cook Medical to receive a breakthrough device designation. It is intended for use in the endovascular treatment of patients with aortic aneurysms.

Calendar of events Please be advised that the events listed opposite, because of COVID-19, are subject to change. Please check the relevant website for further details as the event may be cancelled, postponed, or become a virtual event.

20–26 March Society of Interventional Radiology (SIR) 2021 Annual Meeting Virtual www.sirweb.org

10–13 April European Conference on Interventional Oncology (ECIO) 2021 Virtual

19–22 April CX 2021 Vascular and Endovascular Controversies Digital Edition Virtual www.cxsymposium.com

30 April–2 May Global Embolization and Oncology Symposium Technologies (GEST) 2021 Virtual

9–11 May International Symposium on Endovascular Therapy (ISET) Miami, USA www.iset.org

17–19 June European Conference on Embolotherapy (ET) 2021 Virtual www.cirse.org/events

25–29 September Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Annual Meeting 2021 Lisbon, Portugal www.cirse.org/events/cirse2021

4–7 October CX Aortic Vienna Vienna, Austria www.cxsymposium.org

www.gestweb.org

www.ecio.org

Mar

Issue

19 73

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Interventional News is a trusted, independent source of news and opinion in the interventional world.

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(Ethiodized Oil) Injection

Peripheral Microcatheter

THE COMPATIBLE PAIR For more information, please contact us at 877-729-6679 or customer.service-us@guerbet.com IMPORTANT SAFETY INFORMATION WARNING: FOR INTRALYMPHATIC, INTRAUTERINE AND SELECTIVE HEPATIC INTRA-ARTERIAL USE ONLY See Full Prescribing Information for complete Boxed Warning.

Pulmonary and cerebral embolism can result from inadvertent intravascular injection or intravasation of Lipiodol. Inject Lipiodol slowly with radiologic monitoring; do not exceed recommended dose.

Indication and Usage LIPIODOL® (ethiodized oil) injection is a prescription oil-based radio-opaque contrast agent indicated for: • hysterosalpingography in adults • lymphography in adult and pediatric patients • selective hepatic intra-arterial use for imaging tumors in adults with known hepatocellular carcinoma (HCC) Contraindications LIPIODOL® is contraindicated in patients with hypersensitivity to LIPIODOL®, hyperthyroidism, traumatic injuries, recent hemorrhage or bleeding.

• LIPIODOL® Hysterosalpingography is contraindicated in pregnancy, acute pelvic inflammatory disease, marked cervical erosion, endocervicitis and intrauterine bleeding, in the immediate pre-or postmenstrual phase, or within 30 days of curettage or conization.

• LIPIODOL® Lymphography is contraindicated in patients with a right to left cardiac shunt, advanced pulmonary disease, tissue trauma or hemorrhage, advanced neoplastic disease with expected lymphatic obstruction, previous surgery interrupting the lymphatic system, radiation therapy to the examined area.

• LIPIODOL® Selective Hepatic Intra-arterial Injection is contraindicated in the presence of dilated bile ducts unless external biliary drainage was performed before injection.

Warnings and Precautions • Pulmonary and cerebral embolism may occur immediately or after a few hours to days from inadvertent systemic vascular injection or intravasation of LIPIODOL®. Avoid use in patients with severely impaired lung function, cardiorespiratory failure or right-sided cardiac overload.

• Anaphylactoid and anaphylactic reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following LIPIODOL® administration. Avoid use in patients with a history of sensitivity to other iodinated contrast agents, bronchial asthma or allergic disorders because of an increased risk of a hypersensitivity reaction to LIPIODOL®.

• LIPIODOL® hepatic intra-arterial administration can exacerbate chronic liver disease.

• Iodinated contrast media can affect thyroid function because of the iodide content and can cause hyperthyroidism or hypothyroidism.

Adverse Reactions • Hysterosalpingography – Abdominal pain, foreign body reactions, exacerbation of pelvic inflammatory disease, salpingitis or pelvic peritonitis have been reported after the examination in case of latent infection.

• Lymphography – Lymphangitis, thrombophlebitis, edema or exacerbation of preexisting lymphedema, dyspnea and cough, iodism, allergic dermatitis, lipogranuloma, delayed healing at the site of incision.

• Selective Hepatic Intra-arterial Injection – Abdominal pain, nausea, and vomiting are the most

common reactions; other reactions include hepatic vein thrombosis, hepatic ischemia, liver enzymes abnormalities, transitory decrease in liver function, liver decompensation and renal insufficiency. Procedural risks include vascular complications and infections.

Use in Specific Populations • Pregnancy: The use of LIPIODOL® before or during pregnancy may interfere with thyroid function in both the pregnant woman and her fetus and may affect fetal development. Untreated hypothyroidism in pregnancy is associated with adverse perinatal outcomes, such as spontaneous abortion, preeclampsia, preterm birth, abruptio placentae, and fetal death. The use of LIPIODOL® before or during pregnancy causes iodide transfer across the placenta which may interfere with fetal thyroid function and may affect fetal development. Untreated hypothyroidism is also associated with increased fetal risk of low birth weight, fetal distress, and impaired neuropsychological development. Consider thyroid function testing during pregnancy if a woman was exposed to LIPIODOL® either before or during pregnancy, and also in infants whose mothers were exposed to LIPIODOL® before and during pregnancy or if clinically indicated.

• Pregnancy Testing: Confirm that the patient has a negative pregnancy test within 24 hours before LIPIODOL® administration for hysterosalpingography.

• Lactation: The use of LIPIODOL® may increase the concentration of iodide in human milk and may interfere with the thyroid function of the breastfed infant. Consider thyroid function testing in a breastfed infant whose mother was exposed to LIPIODOL® or if clinically indicated.

• Pediatric: For lymphography use a dose of minimum of 1 mL to a maximum of 6 mL according to the anatomical area to be visualized. Do not exceed 0.25 mL/kg. Administer the smallest possible amount of LIPIODOL® according to the anatomical area to be visualized.

• Geriatric: There are no studies conducted in geriatric patients.

• Renal Impairment: Prior to an intra-arterial administration of LIPIODOL® screen all patients for renal dysfunction by obtaining history and/or laboratory tests. Consider follow-up renal function assessments for patients with a history of renal dysfunction.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

LIPIODOL® is a registered trademark of Guerbet and is available by prescription only.

DraKon™ is Class II medical device intended for use by interventional radiologists and interventional oncologists for the infusion of contrast media into all peripheral vessels, for drug infusion in intra-arterial therapy, and for infusion of embolic materials. Drakon™ should not be used in cerebral vessels. For complete information about precautions and optimal usage conditions for this device, we recommend consulting the instructions for use supplied with each device or with your local Guerbet representative(s).

Revised: 6/2020

GU06201142